No effect of acute exercise on the dynamic change in the expression of genes involved in epigenetic modification in professional athletes

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Exercise can change the expression of individual genes due to changes in the degree of DNA methylation, changes in miRNA expression, or through methylation or acetylation of histones. Hypothesis: Acute exercise increases the expression of genes such as HDAC1, DNMT1, and JHDM1D that can affect epigenetic modifications in PBMCs. Methods: The aim of this study was to determine whether there was a change in gene expression in the blood cells during acute exercise and after a 1-hour recovery. The transcriptions of genes involved in epigenetic modifications (HDAC1, HDAC1 and JHDM1D) were examined in 9 professional athletes at rest, during consecutive stages of a treadmill exercise until exhaustion, and following recovery. Results: No significant differences in the level of transcript were observed in the course of the experiment in the tested PBMC cells. On the other hand, a significant (p = 0.007) correlation was observed in the level of the JHDM1D gene transcript and the number of monocytes in the samples obtained after reaching peak exercise intensity, but in the initial samples this correlation was not significant (p = 0.053). Conclusion: Acute physical exercise does not rapidly alter the transcript levels of the JHDM1D, DNMT1 and HDAC1 genes in PBMCs. The observed correlation between the level of JHDM1D mRNA and the level of monocytes and HDAC1 with lymphocytes requires further investigation. Molecular Genetics Molecular Biology exercise expression hdac1 jhdm1d genes level Figures Figure 1 Introduction Gene expression is influenced by epigenetic modifications as well as DNA sequences. Both biological and environmental factors induce these modifications. One of these factors is exercise (acute and chronic) that can alter the expression of individual genes due to changes in the degree of DNA methylation, changes in miRNA expression, or through methylation or acetylation of histones (Ling and Rönn 2014 ; Simmonds and Seebacher 2017 ; Grazioli et al. 2017 ; Basso and Suzuki). Higher levels of global methylation were found in people exercising 26-30 minutes per day compared to people exercising only 10 minutes per day. However, the increase in methylation was statistically insignificant following multivariate adjustment for age, gender, BMI, and other data (Hughes et al. 2011 ). A 6-month exercise training increased the level of methylation in adipose tissue (Rönn et al. 2013 ) and decreased the level of global methylation in peripheral blood mononuclear cells (PBMC) (Dimauro et al. 2016 ) and muscle tissue (Barrès et al. 2012 ). DNA methylation and histone acetylation and their effect on gene expression during single exercise and training were intensively explored. However, relatively little is known about histone methylation and its impact on gene expression during exercise. Some data is available on the effect of acute exercise on histone methyltransferase (HMT), such as protein arginine methyltransferase ( PRMT) , or the effect of exercise on methylation of specific regions, such as the H3K36 region. The methyl group can be removed from this region by the demethylases having a JmjC domain, such as the HMT of the JmjC domain-containing histone demethylation protein 1 group ( JHDM1 ) (Dimauro et al. 2020 ). The potential changes in DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression during exercise appear to be interesting. The transcription of DNMT1 in PBMCs is relatively constant and its expression linearly declines with age (Ciccarone et al. 2016 ). It is of interest to explore the effect of acute exercise on DNMT1 transcriptions. Considering studies that show that interleukin-6 (IL-6) stimulated cells upregulated DNMT1 expression, and the release of IL-6 is observed during exercise and inflammation(Horsburgh et al. 2015 ), we can expect increased DNMT1 expression during acute exercise. The same is true for Sirtuin 1 (SIRT1) deacetylase which reduces SIRT1’s activity and expression under the influence of oxidative stress. Then, SIRT1 affects the acetylation of the promoter region of the DNMT1 gene, i.e. the expression of this gene (Dimauro et al. 2020 ). Histone deacetylases (HDAC) are an interesting class of enzymes which indirectly influence the development and function of muscles, e.g. by affecting myocyte enhancer factor-2 (MEF2) (McGee and Hargreaves 2004 )and myoblast determination protein 1 ( MyoD ) (Mal et al. 2001 ). The research on the effects of exercise on histone deacetylases primarily focused on class IIa HDAC . Class IIa nuclear export of HDAC under the influence of exercise, and HDAC 3 impact on skeletal muscle adaptation after exercise, by acetylation of histones in the nucleus, were observed (McGee et al. 2009 ). Moreover HDAC 5 can regulate MEF-2 and Glucose transporter type 4 (GLUT4) in response to exercise in muscle cells by exporting HDAC5 from the testicle, not changing its quantity(McGee and Hargreaves 2004 ). Stable expression of HDAC1 in PBMC prompts the investigation of whether acute exercise affects transcription of this gene. It may also be interesting to check the expression of some enzymes responsible for epigenetic control in the blood, as most research focused on muscle or fat tissue. In our study, we selected genes with documented expression in blood mononuclear cells (Nawrocki et al. 2015 , 2017 ) i.e. DNMT1 , HDAC1 , and JHDM1D genes. Most studies on athletes focused on muscle and fat cells. The aim of this study was to determine whether there is a change in gene expression in the blood cells during acute exercise and after a 1-hour recovery. We hypothesized that acute exercise increases the expression of genes HDAC1, DNMT1, and JHDM1D that can affect epigenetic modifications in PBMCs. Methods Nine professional triathletes were invited to participate in the research conducted at the Poznan University of Physical Education in Poznań. The group consisted of adult men aged 23.8 ± 3.4 years with training experience of 9.7±1.6 years. The weight, height and BMI of the athletes were 74.1±6.4 kg, 180.2±5.4 cm, and 22.56±2.33 kg/m 2 , respectively. All participants were informed about the purpose and protocol of the study and signed a written consent. The project was approved by the Ethics Committee at the Poznan University of Medical Sciences (Poznań, Poland) and implemented in accordance with the Helsinki Declaration. Exercise test Two days before the visit to the laboratory, the athletes reduced the amount and intensity of their training. All measurements were performed in the morning, about 2 hours after a light breakfast. First, weight and height were measured using the SECA 285 measuring station (SECA GmbH, Hamburg, Germany). Then, subjects performed an incremental treadmill test until exhaustion on the h/p Cosmos Pulsar treadmill (Sports & Medical GmbH, Nussdorf-Traunstein, Germany). After application of the necessary equipment, once on the treadmill, the athlete stood still on the treadmill for 3 minutes to record resting parameters and check the functioning of the measuring system. The initial speed was set at 4 km‧h −1 and after 3 minutes increased to 8 km‧h −1 . After that point, the speed of the moving strip was progressively increasing by 2 km‧h −1 every 3 minutes until voluntary exhaustion. The main part of the test was followed by a 30-minutes recovery phase consisting in walking at a speed of 4 km‧h −1 for 3 minutes and then sitting for another 27 minutes. During the test, a number of cardiorespiratory variables were measured constantly (breath by breath) using the MetMax 3b-R2 ergospirometer and analyzed using the MetaSoft Studio 5.1.0 software package (Cortex Biophysik GmbH, Leipzig, Germany). Heart rate was measured continuously with the Polar Bluetooth Smart H6 monitor (Polar Electro Oy, Kempele, Finland). The whole measuring system was calibrated according to the manufacturers' instructions. During the measurements, constant ambient temperature was kept at 20-21°C. At the final stage of the test, maximal oxygen uptake (V̇O 2 max) and the values of accompanying cardiorespiratory variables were determined. V̇O 2 max was considered achieved if at least three of the following criteria were met: (i) a plateau in V̇O 2 despite an increase in speed and minute ventilation; (ii) blood lactate concentration ≥9 mmol‧l −1 ; (iii) respiratory exchange ratio ≥1.10; and (iv) heart rate ≥95% of the age-predicted maximum heart rate (Edvardsen et al. 2014 ). Blood sampling Blood samples were obtained via peripheral catheter 1.3 x 32 mm (BD Venflon Pro, Becton Dickinson, Helsingborg, Sweden) inserted retrogradely into the antecubital vein which was kept patent with isotonic saline (0.9% NaCl) during the entire procedure. The blood for molecular analysis was collected into tubes with EDTA (S-monovette K3 EDTA, 7.5 mL, Sarstedt, Nümbrecht, Germany). For lactate concentration measurement, lithium heparin was used as an anticoagulant (S-monovette, 2.7 mL KE, Sarstedt, Nümbrecht, Germany). Lactate in whole blood (20 µL) was immediately assayed using the spectrophotometric enzymatic method (Biosen C-line, EKF Diagnostics, Barleben, Germany). Blood samples were drawn 12 times: at rest (before the test), at the end of each 3-minute stage beginning from the 10 km⋅h −1 , and then during the recovery phase. Detailed timing of blood sampling is presented in Table 1 . Table 1 The timing of the collection of blood samples Collection point Test stage Total time (min) 1 At rest (before the test) 0 2 Running ‒ at 10 km/h 12 3 ‒ at 12 km/h 15 4 ‒ at 14 km/h 18 5 ‒ at 16 km/h 21 6 ‒ at 18 km/h 24 7 Test termination (exhaustion) 24-27* 8 Recovery ‒ 5 minutes 32 9 ‒ 10 minutes 37 10 ‒15 minutes 42 11 ‒ 20 minutes 52 12 ‒ 30 minutes 62 * The range is due to different levels of aerobic capacity and exercise tolerance of individual athletes. Isolation of PBMC and RNA On the day of blood sampling, PBMCs were isolated using a Ficoll density gradient (Lu et al. 2015 ). 3 ml of blood was applied gently to 1.5 ml of Ficoll solution (from Sigma) in a 15 ml tube so that the layers did not mix. The samples were centrifuged for 35 minutes at 400 g at room temperature. The resulting PBMC-containing interphase was transferred to a new tube and washed 3 times in PBS. Washing was performed by adding 2 ml PBS, vortexing, centrifuging for 10 minutes at 340 g and discarding the supernatant. Finally, the pellet in PBS was transferred to a centrifuge tube and subjected to final centrifugation for 10 minutes at 250g. The obtained pellet was suspended in Trizol (RiboEx® GeneAll) and frozen at -80˚C. Further RNA was isolated from the obtained PBMCs according to the protocol of the manufacturer of the RiboEX® reagent from point three. The manufacturer allows the storage of the isolated cells in the RiboEX reagent at -80˚C, which takes place in the second step. The quality and concentration of the obtained RNA were checked on an agarose gel under denaturing conditions and by measuring the absorption spectrum on the NanoDrop apparatus. RT-PCR and qPCR The obtained RNA samples were reverse transcribed into cDNA using M-MLV Reverse Transcriptase® (Invitrogen). The reactions were performed according to the manufacturer's protocol. An equal concentration of templates in each reaction was prepared for RT-PCR reactions in the amount of 100 ng RNA. From each performed reaction, 1 µl of cDNA was collected for the pooled standard sample to derive the standard curves. HDAC1 , DNMT1 , and JHDM1D were selected as test genes, and Esterase D (ESD) andPorphobilinogen deaminase (PBGD) genes were selected for internal control and as a reference to assess the relative amount. The matrices for these genes are presented in the table. Table 2 Primer sequences Gene Sequence (5′–3′) Product size (bp) DNMT1 F: GATGAGAAGAAGCACAGAAGT R: TCTTTGGGGGTCGTTTTGCG 149 HDAC1 F: GAGACGGGATTGATGACGA R: TGAGCCACACTGTAAGACC 104 JHDM1D F: TCCCTTCACCTACATTTTCTG R: TGCCTGCCTCGCCACATC 89 ESD F: ACCACCAAAGGCAGAAACAG R: GGAGCAATGACAACAAGACC 135 PBGD F: GCCAAGGACCAGGACATC R: TCAGGTACAGTTGCCCATC 160 Real-time PCR reactions were performed using "5X Hot Fire Eva Green qPCR Mix" ® and the manufacturer's reaction protocol. Light Cycler 480 Real-time PCR by ROCHE was used for the reaction (check carefully). Agarose gel electrophoresis was performed to check the specificity of the amplification products obtained. Statistical analysis The normality of the distribution was checked with the Shapiro-Wilk test, and then the correlation matrix was used to assess the significance of the related data. Statistical analyses were performed using the STATISTICA 13 software. Results Maximal oxygen uptake (V̇O 2 max) in the tested athletes was 4,96±0,49 l/min/kg, and the maximal heart rate (HRmax) was 187,9±6,47 bpm. The level of lactate was also measured in the examined subjects: it was 1,02±0,19 mmol/l at rest, 10,29±1,59 mmol at exhaustion and 4,16±1,73 mmol/l after 30 minutes of recovery. When analyzing changes in gene expression during incremental exercise, one can see an initial decrease in the amount of transcript of the studied genes, followed by an increase and subsequent fluctuations in the level of the transcript. However, taking into account the standard deviations and the coefficients of variation, the changes in expression seem to be more of an individual matter. A potential tendency would have to be confirmed on a larger sample of participants. Table3 mRNA concentration of individual genes during progressive exercise until exhaustion and 30-min post-exercise recovery In further stages of the statistical analysis, the results of expression obtained from individual athletes were correlated with the biochemical data. Among the average levels of transcripts of given genes in individual athletes, the values of JHDM1D mRNA in athletes 3 and 4 are outliers, being about three times higher than in the other subjects. Several parameters were found, where Athletes 3 and 4 stood out from all athletes on the basis of biochemical data. Athletes 3 and 4 had elevated monocytes compared to all subjects both in the rest phase (MonRest) and after reaching the maximum speed (MonMax). Some parameters, such as the level of monocytes, were assessed only at rest (collection point 1) and at maximum speed (collection point 7). In athletes 3 and 4, the number of lymphocytes (LymRest, LymMax), the number of thrombocytes (PltRest, PltMax), the average volume of platelets (MPVRest, MPVMax) and procalcitonin (PCTRest, PCTMax) were different from the mean resting value. However, these values came from two different poles, where one athlete had the highest value in his pool, while the other had the lowest value in another pool. The correlation of the transcript level with all available parameters of athletes was also checked. It was checked whether the level of transcripts at rest (before exercise), after running at maximum speed, and the difference between these conditions correlated with the available parameters. The parameters of monocytes at maximum velocity, i.e. the value of MonMax with the statistical significance (p = 0.007), correlated with the value of JHDM1D Max at the level of 0.82. The values of MonRest and JHDM1D Rest and the differences between the values at rest and at exhaustion did not give significant results (p > 0.05) with high correlation. The correlation MonRest and JHDM1DRest was 0.6598 (p = 0.053), and for the Rest-Max difference, the correlation was -0.2122 (p = 0.584). A significant correlation was observed between the change in the amount of HDAC1 transcript from resting conditions to maximum speed and the change in the number of lymphocytes at the same time. The number of increased lymphocytes during exercise was inversely proportional to the HDAC1 transcript level. Correlation was -0,7645 (p = 0.016 ) Discussion Many studies involving various exercise protocols have been conducted on the effect of acute exercise and training periods on the changes in genome methylation and gene expression. The changes in expression at two moments were usually reported, i.e. before and after a single exercise, e.g. a marathon run. Research conducted so far has primarily focused on tissues that undergo significant changes, i.e. muscle and fat(McGee and Hargreaves 2011 ; Ling and Rönn 2014 ; Dimauro et al. 2020 ). However, changes in blood cells were also studied (Horsburgh et al. 2015 ; Hunter et al. 2019 ). Available research demonstrated a global decrease or increase in DNA methylation depending on the tissue, suggesting that the proteins responsible for methylation and demethylation change their activity, whether through activating factors or increasing the expression of genes encoding methylases and demethylases (Dimauro et al. 2020 ). It was observed in many studies that physical exercise causes hypermethylation of the genome in adipose tissue. In muscle tissue, acute exercise induces hypomethylation of numerous genes responsible for mitochondrial function. Chronic exercise induces genetic adaptation of a muscle through demethylation of genes involved in mitochondrial, lipid and glucose metabolism, muscle growth and angiogenesis (Dimauro et al. 2020 ). This may demonstrate that exercise stimulates muscle tissue cells to intensify their activity, but the activity of adipose tissue cells is reduced. In contrast, studies on blood cells showed a reduction in global methylation in PBMCs with exercise (Hunter et al. 2019 ). Despite the epigenetic changes observed in the literature, the results obtained in this study indicate that acute exercise has no effect on the production of DNMT1 , HDAC1 and JHDM1D mRNA in PBMC cells. Increased levels of DNMT1 mRNA can be expected based on an increase in DNMT1 mRNA production by IL-6 (Hodge et al. 2007 , p. 1; Horsburgh et al. 2015 ) and the fact that IL-6 is released from the general circulation by acute exercise(Fischer 2006 ). However, the lack of effect of exercise on DNMT1 transcription in PBMCs was observed in the work of D.J. Hunter et al. (Hunter et al. 2019 ). The observed global DNA hypomethylation in PBMCs after acute exercise probably did not involve the DNMT1 gene and was independent of this demethylase (Hunter et al. 2019 ). Histone methylation, depending on the type and position of methylated amino acids, can affect gene expression, for example by activating transcription (Ntanasis-Stathopoulos et al. 2013 ). One of the first observed differences between acetylation and methylation of histones was that methylation increased the basicity and hydrophobicity of the histones, and hence tightened DNA packing and reduced the expression(Rice and Allis 2001 ). Later, it was observed that acute exercise contributed to a change in the degree of methylation of some histones, such as increased lysine methylation in histone H3-k36 in skeletal muscle in nonathletic men (Naghavi Moghadam et al. 2019 ). Histone methyltransferase PRMT (protein arginine methyltransferase) is responsible for arginine methylation, which may contribute to activation or repression of gene expression. The expression and activity of this enzyme do not change under the influence of severe exercise, but its subcellular location changes, namely it moves to the nucleus where the degree of histone methylation increases (Barrès et al. 2012 ). On the other hand, one of the proteins responsible for lysine demethylation is JHDM1D (JmjC domain-containing histone demethylase 1D) that acts, among others, on histone H3k36 (Klose et al. 2006 ). Due to the lack of observed differences in the transcription of JHDM1D in our athletes we examined, it can be assumed that during acute exercise the gene is not subject to increased expression and possible subcellular translocation, as it is the case in a large number of enzymes involved in epigenetic modification(McGee and Hargreaves 2004 ; McGee et al. 2009 ; Horsburgh et al. 2015 ). Myoblast determination protein 1 ( MyoD ) is one of the proteins that affect the development and repair of skeletal muscle. It was shown that it has greater expression in humans after acute exercise than without exercise (Caldow et al. 2015 ). Also, acute exercise increased MyoD expression before and after a 12-week resistance training (Mal et al. 2001 ; Kadi et al. 2004 ). HDAC1 has the ability to repress MyoD transcription by maintaining deacetylation (Mal et al. 2001 ). One can also expect that in people who exercise regularly HDAC1 will less interfere with MyoD deacetylation and its transcription in muscle tissue should not increase. In some researches, an increase in HDAC activity in blood after strenuous exercise was observed in obese subjects. The effect of exercise may be linked to epigenetic control of inflammation (Dorneles et al. 2016 ). Moreover, the effect of acute exercise on the reduction of HDAC 2 activity in PBMC (Dorneles et al. 2017 ) was observed. Our study showed that HDAC1 transcription is not altered by acute exercise. In the leukocytes of our athletes, an increase can be seen between the value at rest and after intense exercise. The increase in these leukocytes in the same conditions was also observed by other researchers(Dorneles et al. 2016 ). We could not find any research on the relationship between the effects of exercise on leukocytes and genes. Also, the correlation between the JHDM1D transcript and the level of monocytes and HDAC1 transcript with level of lymphocytes should be confirmed. Further research should focus on the level of proteins encoded by HDAC1, DNMT1 and JHDM1D genes and their subcellular locations. Summary Acute physical exercise does not alter the transcript levels of the JHDM1D , DNMT1 and HDAC1 genes in PBMCs. The observed correlation between the level of JHDM1D mRNA and the level of monocytes and HDAC1 with lymphocytes requires further investigation. References Barrès R, Yan J, Egan B et al (2012) Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab 15:405–411 Basso JC, Suzuki WA The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review.Brain Plast2:127–152. https://doi.org/10.3233/BPL-160040 Caldow MK, Thomas EE, Dale MJ et al (2015) Early myogenic responses to acute exercise before and after resistance training in young men. 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PLoS Genet 9:e1003572 Simmonds AIM, Seebacher F (2017) Histone deacetylase activity modulates exercise-induced skeletal muscle plasticity in zebrafish (Danio rerio). Am J Physiol Regul Integr Comp Physiol 313:R35–R43 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1075362","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":65922676,"identity":"94ca28a8-b0a3-489c-b399-b3b8f22150d8","order_by":0,"name":"Witold Józef Światowy","email":"","orcid":"","institution":"Poznan University of Medical Sciences: Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Witold","middleName":"Józef","lastName":"Światowy","suffix":""},{"id":65922677,"identity":"509309f1-f6b5-4685-9f75-105de2ba5fda","order_by":1,"name":"Jacek Zieliński","email":"","orcid":"","institution":"Akademia Wychowania Fizycznego im Eugeniusza Piaseckiego w Poznaniu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jacek","middleName":"","lastName":"Zieliński","suffix":""},{"id":65922678,"identity":"d67be980-0759-4d93-ac7d-52509a876486","order_by":2,"name":"Maria Aleksandra Osielska","email":"","orcid":"","institution":"Poznan University of Medical Sciences: Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Aleksandra","lastName":"Osielska","suffix":""},{"id":65922679,"identity":"455a06d0-b719-4703-a7df-393bcf7b118c","order_by":3,"name":"Krzysztof Kusy","email":"","orcid":"","institution":"Akademia Wychowania Fizycznego im Eugeniusza Piaseckiego w Poznaniu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Krzysztof","middleName":"","lastName":"Kusy","suffix":""},{"id":65922680,"identity":"42a2551d-d9be-4878-9ae6-1b447b48f1e8","order_by":4,"name":"Dariusz Wieliński","email":"","orcid":"","institution":"Akademia Wychowania Fizycznego im Eugeniusza Piaseckiego w Poznaniu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dariusz","middleName":"","lastName":"Wieliński","suffix":""},{"id":65922681,"identity":"a569f6ae-99ee-4175-b45d-38161e42569d","order_by":5,"name":"Andrzej Pławski","email":"","orcid":"","institution":"Polish Academy of Sciences: Polska Akademia Nauk","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Andrzej","middleName":"","lastName":"Pławski","suffix":""},{"id":65922682,"identity":"a24f99a9-f610-41bf-9648-266e95e948e9","order_by":6,"name":"Paweł Jagodzinski","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYFCCA0DMxsDDD+Exg3ADcVokG+BaGAlpYQBrYTA4QKwWc8bDj198KKuTMb6RnfaAocI6sUG6Eb8Wy4ZjZpYzzrHxmN3I3W7AcCY9sUHmIH4tBgcOmBnztvGAtGyTYGw7nNggkUhIy/FvQC0SPMYzQFr+EaXljPFj3jYDHgMJkJYGIrRYNpwpY5xxLoFH4szb7QYJx9KN2wj5xVzi+OYPwBCz52/P3fbgQ421bL908wH8DpM4wCYBZbMxJIBICTzKwVr4G5g/wLWAASEto2AUjIJRMOIAAIwoSrGn6B4hAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-9046-6802","institution":"Poznan University of Medical Sciences: Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Paweł","middleName":"","lastName":"Jagodzinski","suffix":""}],"badges":[],"createdAt":"2021-11-12 18:29:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1075362/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1075362/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":16033321,"identity":"c06ee5bd-b746-4eac-87c8-e6b23b4a391d","added_by":"auto","created_at":"2021-11-30 17:45:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":100731,"visible":true,"origin":"","legend":"JHDM1D, DNMT1, and HDAC1 transcript levels in peripheral blood mononuclear cells (PBMCs) in athletes during a progressive exercise until exhaustion and a 30-min post-exercise recovery. The JHDM1D, DNMT1, and HDAC1 mRNA levels were corrected for PBGD and ESD levels. The amounts of JJHDM1D, DNMT1, and HDAC1 mRNA were expressed as the decimal logarithm of multiples of these cDNA copies in the calibrator.","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1075362/v1/6fd4a34b5693ceaf35a5f71b.png"},{"id":17281205,"identity":"f628cea9-dc35-4113-94d2-7b04889e0d6b","added_by":"auto","created_at":"2022-01-13 12:34:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":359963,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1075362/v1/0e94c4c9-a66b-44f3-8c65-b810c98fe9cf.pdf"}],"financialInterests":"","formattedTitle":"No effect of acute exercise on the dynamic change in the expression of genes involved in epigenetic modification in professional athletes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGene expression is influenced by epigenetic modifications as well as DNA sequences. Both biological and environmental factors induce these modifications. One of these factors is exercise (acute and chronic) that can alter the expression of individual genes due to changes in the degree of DNA methylation, changes in miRNA expression, or through methylation or acetylation of histones (Ling and R\u0026ouml;nn \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Simmonds and Seebacher \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Grazioli et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Basso and Suzuki).\u003c/p\u003e \u003cp\u003eHigher levels of global methylation were found in people exercising 26-30 minutes per day compared to people exercising only 10 minutes per day. However, the increase in methylation was statistically insignificant following multivariate adjustment for age, gender, BMI, and other data (Hughes et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). A 6-month exercise training increased the level of methylation in adipose tissue (R\u0026ouml;nn et al. \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2013\u003c/span\u003e) and decreased the level of global methylation in peripheral blood mononuclear cells (PBMC) (Dimauro et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) and muscle tissue (Barr\u0026egrave;s et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDNA methylation and histone acetylation and their effect on gene expression during single exercise and training were intensively explored. However, relatively little is known about histone methylation and its impact on gene expression during exercise. Some data is available on the effect of acute exercise on histone methyltransferase (HMT), such as protein arginine methyltransferase (\u003cem\u003ePRMT)\u003c/em\u003e, or the effect of exercise on methylation of specific regions, such as the H3K36 region. The methyl group can be removed from this region by the demethylases having a JmjC domain, such as the HMT of the JmjC domain-containing histone demethylation protein 1 group (\u003cem\u003eJHDM1\u003c/em\u003e) (Dimauro et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe potential changes in DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression during exercise appear to be interesting. The transcription of \u003cem\u003eDNMT1\u003c/em\u003e in PBMCs is relatively constant and its expression linearly declines with age (Ciccarone et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). It is of interest to explore the effect of acute exercise \u003cem\u003eon DNMT1\u003c/em\u003e transcriptions. Considering studies that show that interleukin-6 (IL-6) stimulated cells upregulated \u003cem\u003eDNMT1\u003c/em\u003e expression, and the release of \u003cem\u003eIL-6\u003c/em\u003e is observed during exercise and inflammation(Horsburgh et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2015\u003c/span\u003e), we can expect increased DNMT1 expression during acute exercise.\u003c/p\u003e \u003cp\u003eThe same is true for Sirtuin 1 (SIRT1) deacetylase which reduces SIRT1\u0026rsquo;s activity and expression under the influence of oxidative stress. Then, SIRT1 affects the acetylation of the promoter region of the DNMT1 gene, i.e. the expression of this gene (Dimauro et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHistone deacetylases (HDAC) are an interesting class of enzymes which indirectly influence the development and function of muscles, e.g. by affecting myocyte enhancer factor-2 (MEF2) (McGee and Hargreaves \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2004\u003c/span\u003e)and myoblast determination protein 1 (\u003cem\u003eMyoD\u003c/em\u003e) (Mal et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). The research on the effects of exercise on histone deacetylases primarily focused on class IIa \u003cem\u003eHDAC\u003c/em\u003e. Class IIa nuclear export of \u003cem\u003eHDAC\u003c/em\u003e under the influence of exercise, and \u003cem\u003eHDAC\u003c/em\u003e3 impact on skeletal muscle adaptation after exercise, by acetylation of histones in the nucleus, were observed (McGee et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2009\u003c/span\u003e). Moreover \u003cem\u003eHDAC\u003c/em\u003e5 can regulate MEF-2 and Glucose transporter type 4 (GLUT4) in response to exercise in muscle cells by exporting HDAC5 from the testicle, not changing its quantity(McGee and Hargreaves \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2004\u003c/span\u003e). Stable expression of HDAC1 in PBMC prompts the investigation of whether acute exercise affects transcription of this gene.\u003c/p\u003e \u003cp\u003eIt may also be interesting to check the expression of some enzymes responsible for epigenetic control in the blood, as most research focused on muscle or fat tissue. In our study, we selected genes with documented expression in blood mononuclear cells (Nawrocki et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2015\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) i.e. \u003cem\u003eDNMT1\u003c/em\u003e, \u003cem\u003eHDAC1\u003c/em\u003e, and \u003cem\u003eJHDM1D\u003c/em\u003e genes.\u003c/p\u003e \u003cp\u003eMost studies on athletes focused on muscle and fat cells. The aim of this study was to determine whether there is a change in gene expression in the blood cells during acute exercise and after a 1-hour recovery. We hypothesized that acute exercise increases the expression of genes HDAC1, DNMT1, and JHDM1D that can affect epigenetic modifications in PBMCs.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eNine professional triathletes were invited to participate in the research conducted at the Poznan University of Physical Education in Poznań. The group consisted of adult men aged 23.8 \u0026plusmn; 3.4 years with training experience of 9.7\u0026plusmn;1.6 years. The weight, height and BMI of the athletes were 74.1\u0026plusmn;6.4 kg, 180.2\u0026plusmn;5.4 cm, and 22.56\u0026plusmn;2.33 kg/m\u003csup\u003e2\u003c/sup\u003e, respectively. All participants were informed about the purpose and protocol of the study and signed a written consent. The project was approved by the Ethics Committee at the Poznan University of Medical Sciences (Poznań, Poland) and implemented in accordance with the Helsinki Declaration.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eExercise test\u003c/h2\u003e \u003cp\u003eTwo days before the visit to the laboratory, the athletes reduced the amount and intensity of their training. All measurements were performed in the morning, about 2 hours after a light breakfast. First, weight and height were measured using the SECA 285 measuring station (SECA GmbH, Hamburg, Germany). Then, subjects performed an incremental treadmill test until exhaustion on the h/p Cosmos Pulsar treadmill (Sports \u0026amp; Medical GmbH, Nussdorf-Traunstein, Germany). After application of the necessary equipment, once on the treadmill, the athlete stood still on the treadmill for 3 minutes to record resting parameters and check the functioning of the measuring system. The initial speed was set at 4 km‧h\u003csup\u003e\u0026minus;1\u003c/sup\u003e and after 3 minutes increased to 8 km‧h\u003csup\u003e\u0026minus;1\u003c/sup\u003e. After that point, the speed of the moving strip was progressively increasing by 2 km‧h\u003csup\u003e\u0026minus;1\u003c/sup\u003e every 3 minutes until voluntary exhaustion. The main part of the test was followed by a 30-minutes recovery phase consisting in walking at a speed of 4 km‧h\u003csup\u003e\u0026minus;1\u003c/sup\u003e for 3 minutes and then sitting for another 27 minutes. During the test, a number of cardiorespiratory variables were measured constantly (breath by breath) using the MetMax 3b-R2 ergospirometer and analyzed using the MetaSoft Studio 5.1.0 software package (Cortex Biophysik GmbH, Leipzig, Germany). Heart rate was measured continuously with the Polar Bluetooth Smart H6 monitor (Polar Electro Oy, Kempele, Finland). The whole measuring system was calibrated according to the manufacturers' instructions. During the measurements, constant ambient temperature was kept at 20-21\u0026deg;C. At the final stage of the test, maximal oxygen uptake (V̇O\u003csub\u003e2\u003c/sub\u003emax) and the values of accompanying cardiorespiratory variables were determined. V̇O\u003csub\u003e2\u003c/sub\u003emax was considered achieved if at least three of the following criteria were met: (i) a plateau in V̇O\u003csub\u003e2\u003c/sub\u003e despite an increase in speed and minute ventilation; (ii) blood lactate concentration \u0026ge;9 mmol‧l\u003csup\u003e\u0026minus;1\u003c/sup\u003e; (iii) respiratory exchange ratio \u0026ge;1.10; and (iv) heart rate \u0026ge;95% of the age-predicted maximum heart rate (Edvardsen et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2014\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eBlood sampling\u003c/h2\u003e \u003cp\u003eBlood samples were obtained via peripheral catheter 1.3 x 32 mm (BD Venflon Pro, Becton Dickinson, Helsingborg, Sweden) inserted retrogradely into the antecubital vein which was kept patent with isotonic saline (0.9% NaCl) during the entire procedure. The blood for molecular analysis was collected into tubes with EDTA (S-monovette K3 EDTA, 7.5 mL, Sarstedt, N\u0026uuml;mbrecht, Germany). For lactate concentration measurement, lithium heparin was used as an anticoagulant (S-monovette, 2.7 mL KE, Sarstedt, N\u0026uuml;mbrecht, Germany). Lactate in whole blood (20 \u0026micro;L) was immediately assayed using the spectrophotometric enzymatic method (Biosen C-line, EKF Diagnostics, Barleben, Germany).\u003c/p\u003e \u003cp\u003eBlood samples were drawn 12 times: at rest (before the test), at the end of each 3-minute stage beginning from the 10 km\u0026sdot;h\u003csup\u003e\u0026minus;1\u003c/sup\u003e, and then during the recovery phase. Detailed timing of blood sampling is presented in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe timing of the collection of blood samples\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCollection point\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTest stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal time (min)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt rest (before the test)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRunning ‒ at 10 km/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e‒ at 12 km/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e‒ at 14 km/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e‒ at 16 km/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e‒ at 18 km/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTest termination (exhaustion)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24-27*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRecovery ‒ 5 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e‒ 10 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e‒15 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e‒ 20 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e‒ 30 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e* The range is due to different levels of aerobic capacity and exercise tolerance of individual athletes.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eIsolation of PBMC and RNA\u003c/h2\u003e \u003cp\u003eOn the day of blood sampling, PBMCs were isolated using a Ficoll density gradient (Lu et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). 3 ml of blood was applied gently to 1.5 ml of Ficoll solution (from Sigma) in a 15 ml tube so that the layers did not mix. The samples were centrifuged for 35 minutes at 400 g at room temperature. The resulting PBMC-containing interphase was transferred to a new tube and washed 3 times in PBS. Washing was performed by adding 2 ml PBS, vortexing, centrifuging for 10 minutes at 340 g and discarding the supernatant. Finally, the pellet in PBS was transferred to a centrifuge tube and subjected to final centrifugation for 10 minutes at 250g. The obtained pellet was suspended in Trizol (RiboEx\u0026reg; GeneAll) and frozen at -80˚C.\u003c/p\u003e \u003cp\u003eFurther RNA was isolated from the obtained PBMCs according to the protocol of the manufacturer of the RiboEX\u0026reg; reagent from point three. The manufacturer allows the storage of the isolated cells in the RiboEX reagent at -80˚C, which takes place in the second step.\u003c/p\u003e \u003cp\u003eThe quality and concentration of the obtained RNA were checked on an agarose gel under denaturing conditions and by measuring the absorption spectrum on the NanoDrop apparatus.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eRT-PCR and qPCR\u003c/h2\u003e \u003cp\u003eThe obtained RNA samples were reverse transcribed into cDNA using M-MLV Reverse Transcriptase\u0026reg; (Invitrogen). The reactions were performed according to the manufacturer's protocol. An equal concentration of templates in each reaction was prepared for RT-PCR reactions in the amount of 100 ng RNA. From each performed reaction, 1 \u0026micro;l of cDNA was collected for the pooled standard sample to derive the standard curves.\u003c/p\u003e \u003cp\u003e \u003cem\u003eHDAC1\u003c/em\u003e, \u003cem\u003eDNMT1\u003c/em\u003e, and \u003cem\u003eJHDM1D\u003c/em\u003e were selected as test genes, and Esterase D (ESD) andPorphobilinogen deaminase (PBGD) genes were selected for internal control and as a reference to assess the relative amount. The matrices for these genes are presented in the table.\u003c/p\u003e \u003cp\u003e \u003cem\u003eTable 2\u003c/em\u003e \u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003ePrimer sequences\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"3\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGene\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSequence (5\u0026prime;\u0026ndash;3\u0026prime;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProduct size (bp)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDNMT1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF: GATGAGAAGAAGCACAGAAGT\u003c/p\u003e \u003cp\u003eR: TCTTTGGGGGTCGTTTTGCG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e149\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eHDAC1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF: GAGACGGGATTGATGACGA\u003c/p\u003e \u003cp\u003eR: TGAGCCACACTGTAAGACC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eJHDM1D\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF: TCCCTTCACCTACATTTTCTG\u003c/p\u003e \u003cp\u003eR: TGCCTGCCTCGCCACATC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF: ACCACCAAAGGCAGAAACAG\u003c/p\u003e \u003cp\u003eR: GGAGCAATGACAACAAGACC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e135\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePBGD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF: GCCAAGGACCAGGACATC\u003c/p\u003e \u003cp\u003eR: TCAGGTACAGTTGCCCATC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e160\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eReal-time PCR reactions were performed using \"5X Hot Fire Eva Green qPCR Mix\" \u0026reg; and the manufacturer's reaction protocol. Light Cycler 480 Real-time PCR by ROCHE was used for the reaction (check carefully). Agarose gel electrophoresis was performed to check the specificity of the amplification products obtained.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe normality of the distribution was checked with the Shapiro-Wilk test, and then the correlation matrix was used to assess the significance of the related data. Statistical analyses were performed\u003c/p\u003e \u003cp\u003eusing the STATISTICA 13 software.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eMaximal oxygen uptake (V̇O\u003csub\u003e2\u003c/sub\u003emax) in the tested athletes was 4,96\u0026plusmn;0,49 l/min/kg, and the maximal heart rate (HRmax) was 187,9\u0026plusmn;6,47 bpm. The level of lactate was also measured in the examined subjects: it was 1,02\u0026plusmn;0,19 mmol/l at rest, 10,29\u0026plusmn;1,59 mmol at exhaustion and 4,16\u0026plusmn;1,73 mmol/l after 30 minutes of recovery.\u003c/p\u003e\n\u003cp\u003eWhen analyzing changes in gene expression during incremental exercise, one can see an initial decrease in the amount of transcript of the studied genes, followed by an increase and subsequent fluctuations in the level of the transcript. However, taking into account the standard deviations and the coefficients of variation, the changes in expression seem to be more of an individual matter. A potential tendency would have to be confirmed on a larger sample of participants.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTable3\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003emRNA concentration of individual genes during progressive exercise until exhaustion and 30-min post-exercise recovery\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cimg 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\"\u003e\u003c/em\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eIn further stages of the statistical analysis, the results of expression obtained from individual athletes were correlated with the biochemical data. Among the average levels of transcripts of given genes in individual athletes, the values of \u003cem\u003eJHDM1D\u003c/em\u003e mRNA in athletes 3 and 4 are outliers, being about three times higher than in the other subjects. Several parameters were found, where Athletes 3 and 4 stood out from all athletes on the basis of biochemical data.\u003c/p\u003e\n\u003cp\u003eAthletes 3 and 4 had elevated monocytes compared to all subjects both in the rest phase (MonRest) and after reaching the maximum speed (MonMax). Some parameters, such as the level of monocytes, were assessed only at rest (collection point 1) and at maximum speed (collection point 7).\u003c/p\u003e\n\u003cp\u003eIn athletes 3 and 4, the number of lymphocytes (LymRest, LymMax), the number of thrombocytes (PltRest, PltMax), the average volume of platelets (MPVRest, MPVMax) and procalcitonin (PCTRest, PCTMax) were different from the mean resting value. However, these values came from two different poles, where one athlete had the highest value in his pool, while the other had the lowest value in another pool.\u003c/p\u003e\n\u003cp\u003eThe correlation of the transcript level with all available parameters of athletes was also checked. It was checked whether the level of transcripts at rest (before exercise), after running at maximum speed, and the difference between these conditions correlated with the available parameters.\u003c/p\u003e\n\u003cp\u003eThe parameters of monocytes at maximum velocity, i.e. the value of MonMax with the statistical significance (p = 0.007), correlated with the value of \u003cem\u003eJHDM1D\u003c/em\u003eMax at the level of 0.82. The values of MonRest and \u003cem\u003eJHDM1D\u003c/em\u003eRest and the differences between the values at rest and at exhaustion did not give significant results (p \u0026gt; 0.05) with high correlation. The correlation MonRest and JHDM1DRest was 0.6598 (p = 0.053), and for the Rest-Max difference, the correlation was -0.2122 (p = 0.584).\u003c/p\u003e\n\u003cp\u003eA significant correlation was observed between the change in the amount of \u003cem\u003eHDAC1\u003c/em\u003e transcript from resting conditions to maximum speed and the change in the number of lymphocytes at the same time. The number of increased lymphocytes during exercise was inversely proportional to the \u003cem\u003eHDAC1\u003c/em\u003e transcript level. Correlation was -0,7645 (p = 0.016 )\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMany studies involving various exercise protocols have been conducted on the effect of acute exercise and training periods on the changes in genome methylation and gene expression. The changes in expression at two moments were usually reported, i.e. before and after a single exercise, e.g. a marathon run. Research conducted so far has primarily focused on tissues that undergo significant changes, i.e. muscle and fat(McGee and Hargreaves \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2011\u003c/span\u003e; Ling and R\u0026ouml;nn \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Dimauro et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). However, changes in blood cells were also studied (Horsburgh et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Hunter et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAvailable research demonstrated a global decrease or increase in DNA methylation depending on the tissue, suggesting that the proteins responsible for methylation and demethylation change their activity, whether through activating factors or increasing the expression of genes encoding methylases and demethylases (Dimauro et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt was observed in many studies that physical exercise causes hypermethylation of the genome in adipose tissue. In muscle tissue, acute exercise induces hypomethylation of numerous genes responsible for mitochondrial function. Chronic exercise induces genetic adaptation of a muscle through demethylation of genes involved in mitochondrial, lipid and glucose metabolism, muscle growth and angiogenesis (Dimauro et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). This may demonstrate that exercise stimulates muscle tissue cells to intensify their activity, but the activity of adipose tissue cells is reduced. In contrast, studies on blood cells showed a reduction in global methylation in PBMCs with exercise (Hunter et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Despite the epigenetic changes observed in the literature, the results obtained in this study indicate that acute exercise has no effect on the production of \u003cem\u003eDNMT1\u003c/em\u003e, \u003cem\u003eHDAC1\u003c/em\u003e and \u003cem\u003eJHDM1D\u003c/em\u003e mRNA in PBMC cells.\u003c/p\u003e \u003cp\u003eIncreased levels of \u003cem\u003eDNMT1\u003c/em\u003e mRNA can be expected based on an increase in \u003cem\u003eDNMT1\u003c/em\u003e mRNA production by \u003cem\u003eIL-6\u003c/em\u003e (Hodge et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2007\u003c/span\u003e, p. 1; Horsburgh et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) and the fact that \u003cem\u003eIL-6\u003c/em\u003e is released from the general circulation by acute exercise(Fischer \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). However, the lack of effect of exercise on \u003cem\u003eDNMT1\u003c/em\u003e transcription in PBMCs was observed in the work of D.J. Hunter et al. (Hunter et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). The observed global DNA hypomethylation in PBMCs after acute exercise probably did not involve the \u003cem\u003eDNMT1\u003c/em\u003e gene and was independent of this demethylase (Hunter et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHistone methylation, depending on the type and position of methylated amino acids, can affect gene expression, for example by activating transcription (Ntanasis-Stathopoulos et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). One of the first observed differences between acetylation and methylation of histones was that methylation increased the basicity and hydrophobicity of the histones, and hence tightened DNA packing and reduced the expression(Rice and Allis \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). Later, it was observed that acute exercise contributed to a change in the degree of methylation of some histones, such as increased lysine methylation in histone H3-k36 in skeletal muscle in nonathletic men (Naghavi Moghadam et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Histone methyltransferase PRMT (protein arginine methyltransferase) is responsible for arginine methylation, which may contribute to activation or repression of gene expression. The expression and activity of this enzyme do not change under the influence of severe exercise, but its subcellular location changes, namely it moves to the nucleus where the degree of histone methylation increases (Barr\u0026egrave;s et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). On the other hand, one of the proteins responsible for lysine demethylation is \u003cem\u003eJHDM1D\u003c/em\u003e (JmjC domain-containing histone demethylase 1D) that acts, among others, on histone H3k36 (Klose et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). Due to the lack of observed differences in the transcription of \u003cem\u003eJHDM1D\u003c/em\u003e in our athletes we examined, it can be assumed that during acute exercise the gene is not subject to increased expression and possible subcellular translocation, as it is the case in a large number of enzymes involved in epigenetic modification(McGee and Hargreaves \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2004\u003c/span\u003e; McGee et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Horsburgh et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2015\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMyoblast determination protein 1 (\u003cem\u003eMyoD\u003c/em\u003e) is one of the proteins that affect the development and repair of skeletal muscle. It was shown that it has greater expression in humans after acute exercise than without exercise (Caldow et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Also, acute exercise increased MyoD expression before and after a 12-week resistance training (Mal et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2001\u003c/span\u003e; Kadi et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2004\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cem\u003eHDAC1\u003c/em\u003e has the ability to repress \u003cem\u003eMyoD\u003c/em\u003e transcription by maintaining deacetylation (Mal et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). One can also expect that in people who exercise regularly \u003cem\u003eHDAC1\u003c/em\u003e will less interfere with \u003cem\u003eMyoD\u003c/em\u003e deacetylation and its transcription in muscle tissue should not increase. In some researches, an increase in \u003cem\u003eHDAC\u003c/em\u003e activity in blood after strenuous exercise was observed in obese subjects. The effect of exercise may be linked to epigenetic control of inflammation (Dorneles et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Moreover, the effect of acute exercise on the reduction of \u003cem\u003eHDAC\u003c/em\u003e2 activity in PBMC (Dorneles et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) was observed. Our study showed that \u003cem\u003eHDAC1\u003c/em\u003e transcription is not altered by acute exercise.\u003c/p\u003e \u003cp\u003eIn the leukocytes of our athletes, an increase can be seen between the value at rest and after intense exercise. The increase in these leukocytes in the same conditions was also observed by other researchers(Dorneles et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). We could not find any research on the relationship between the effects of exercise on leukocytes and genes. Also, the correlation between the \u003cem\u003eJHDM1D\u003c/em\u003e transcript and the level of monocytes and \u003cem\u003eHDAC1\u003c/em\u003e transcript with level of lymphocytes should be confirmed. Further research should focus on the level of proteins encoded by HDAC1, DNMT1 and JHDM1D genes and their subcellular locations.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSummary\u003c/h2\u003e \u003cp\u003eAcute physical exercise does not alter the transcript levels of the \u003cem\u003eJHDM1D\u003c/em\u003e, \u003cem\u003eDNMT1\u003c/em\u003e and \u003cem\u003eHDAC1\u003c/em\u003e genes in PBMCs. The observed correlation between the level of \u003cem\u003eJHDM1D\u003c/em\u003e mRNA and the level of monocytes and \u003cem\u003eHDAC1\u003c/em\u003e with lymphocytes requires further investigation.\u003c/p\u003e \u003c/div\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBarr\u0026egrave;s R, Yan J, Egan B et al (2012) Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab 15:405\u0026ndash;411\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBasso JC, Suzuki WA The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review.Brain Plast2:127\u0026ndash;152. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3233/BPL-160040\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCaldow MK, Thomas EE, Dale MJ et al (2015) Early myogenic responses to acute exercise before and after resistance training in young men. Physiol Rep 3:e12511\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCiccarone F, Malavolta M, Calabrese R et al (2016) Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK‐AGE study. Aging Cell 15:755\u0026ndash;765\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDimauro I, Paronetto MP, Caporossi D (2020) Exercise, redox homeostasis and the epigenetic landscape. Redox Biol 35:101477\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDimauro I, Scalabrin M, Fantini C et al (2016) Resistance training and redox homeostasis: Correlation with age-associated genomic changes. Redox Biol 10:34\u0026ndash;44\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDorneles GP, Boeira MCR, Schipper LL et al (2017) Acute Strenuous Exercise Induces an Imbalance on Histone H4 Acetylation/Histone Deacetylase 2 and Increases the Proinflammatory Profile of PBMC of Obese Individuals. Oxidative Medicine and Cellular Longevity 2017:e1530230. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2017/1530230\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDorneles GP, da Silva IRV, Korb A et al (2016) High intensity interval exercise enhances the global HDAC activity in PBMC and anti-inflammatory cytokines of overweight-obese subjects. Obesity Medicine 2:25\u0026ndash;30\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEdvardsen E, Hem E, Anderssen SA (2014) End criteria for reaching maximal oxygen uptake must be strict and adjusted to sex and age: a cross-sectional study. PLoS ONE 9:e85276\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFischer CP (2006) Interleukin-6 in acute exercise and training: what is the biological relevance?Exerc Immunol Rev12:6\u0026ndash;33\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrazioli E, Dimauro I, Mercatelli N et al (2017) Physical activity in the prevention of human diseases: role of epigenetic modifications. BMC Genomics 18:802\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHodge DR, Cho E, Copeland TD et al (2007) IL-6 enhances the nuclear translocation of DNA cytosine-5-methyltransferase 1 (DNMT1) via phosphorylation of the nuclear localization sequence by the AKT kinase.Cancer Genomics Proteomics4:387\u0026ndash;398\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHorsburgh S, Todryk S, Toms C et al (2015) Exercise-conditioned plasma attenuates nuclear concentrations of DNA methyltransferase 3B in human peripheral blood mononuclear cells. Physiological Reports 3:e12621\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHughes LAE, Simons CCJM, van den Brandt PA et al (2011) Body Size, Physical Activity and Risk of Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP). PLoS ONE 6:e18571\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHunter DJ, James L, Hussey B et al (2019) Impact of aerobic exercise and fatty acid supplementation on global and gene-specific DNA methylation. Epigenetics 14:294\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKadi F, Johansson F, Johansson R et al (2004) Effects of one bout of endurance exercise on the expression of myogenin in human quadriceps muscle. Histochem Cell Biol 121:329\u0026ndash;334\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlose RJ, Kallin EM, Zhang Y (2006) JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet 7:715\u0026ndash;727\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLing C, R\u0026ouml;nn T (2014) Epigenetic adaptation to regular exercise in humans. Drug Discovery Today 19:1015\u0026ndash;1018\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu Y, Ahmed S, Harari F, Vahter M (2015) Impact of Ficoll density gradient centrifugation on major and trace element concentrations in erythrocytes and blood plasma. J Trace Elem Med Biol 29:249\u0026ndash;254\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMal A, Sturniolo M, Schiltz RL et al (2001) A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program. EMBO J 20:1739\u0026ndash;1753\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGee SL, Fairlie E, Garnham AP, Hargreaves M (2009) Exercise-induced histone modifications in human skeletal muscle. J Physiol 587:5951\u0026ndash;5958\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGee SL, Hargreaves M (2004) Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle. Diabetes 53:1208\u0026ndash;1214\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGee SL, Hargreaves M (2011) Histone modifications and exercise adaptations. J Appl Physiol (1985) 110:258\u0026ndash;263\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaghavi Moghadam AA, Shiravand M, Rezapour S et al (2019) Effect of a session of intensive exercise with ginseng supplementation on histone H3 protein methylation of skeletal muscle of nonathlete men. Mol Genet Genomic Med 7:e651\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNawrocki MJ, Majewski D, Puszczewicz M, Jagodziński PP (2017) Decreased mRNA expression levels of DNA methyltransferases type 1 and 3A in systemic lupus erythematosus. Rheumatol Int 37:775\u0026ndash;783\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNawrocki MJ, Strugała AJ, Piotrowski P et al (2015) JHDM1D and HDAC1-3 mRNA expression levels in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Z Rheumatol 74:902\u0026ndash;910\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNtanasis-Stathopoulos I, Tzanninis I-G, Philippou A, Koutsilieris M (2013) Epigenetic regulation on gene expression induced by physical exercise.Journal of musculoskeletal \u0026amp; neuronal interactions13:133\u0026ndash;146\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRice JC, Allis CD (2001) Histone methylation versus histone acetylation: new insights into epigenetic regulation. Curr Opin Cell Biol 13:263\u0026ndash;273\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eR\u0026ouml;nn T, Volkov P, Daveg\u0026aring;rdh C et al (2013) A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet 9:e1003572\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimmonds AIM, Seebacher F (2017) Histone deacetylase activity modulates exercise-induced skeletal muscle plasticity in zebrafish (Danio rerio). Am J Physiol Regul Integr Comp Physiol 313:R35\u0026ndash;R43\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"exercise, expression, hdac1, jhdm1d, genes, level","lastPublishedDoi":"10.21203/rs.3.rs-1075362/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1075362/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground:\u003c/p\u003e\u003cp\u003eThe adaptation of the organism to exercise in the context of gene expression profile is an interesting phenomenon. Exercise can change the expression of individual genes due to changes in the degree of DNA methylation, changes in miRNA expression, or through methylation or acetylation of histones.\u003c/p\u003e\u003cp\u003eHypothesis:\u003c/p\u003e\u003cp\u003eAcute exercise increases the expression of genes such as HDAC1, DNMT1, and JHDM1D that can affect epigenetic modifications in PBMCs.\u003c/p\u003e\u003cp\u003eMethods:\u003c/p\u003e\u003cp\u003eThe aim of this study was to determine whether there was a change in gene expression in the blood cells during acute exercise and after a 1-hour recovery. The transcriptions of genes involved in epigenetic modifications (HDAC1, HDAC1 and JHDM1D) were examined in 9 professional athletes at rest, during consecutive stages of a treadmill exercise until exhaustion, and following recovery.\u003c/p\u003e\u003cp\u003eResults:\u003c/p\u003e\u003cp\u003eNo significant differences in the level of transcript were observed in the course of the experiment in the tested PBMC cells. On the other hand, a significant (p = 0.007) correlation was observed in the level of the JHDM1D gene transcript and the number of monocytes in the samples obtained after reaching peak exercise intensity, but in the initial samples this correlation was not significant (p = 0.053).\u003c/p\u003e\u003cp\u003eConclusion:\u003c/p\u003e\u003cp\u003eAcute physical exercise does not rapidly alter the transcript levels of the JHDM1D, DNMT1 and HDAC1 genes in PBMCs. The observed correlation between the level of JHDM1D mRNA and the level of monocytes and HDAC1 with lymphocytes requires further investigation.\u003c/p\u003e","manuscriptTitle":"No effect of acute exercise on the dynamic change in the expression of genes involved in epigenetic modification in professional athletes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-11-30 17:45:18","doi":"10.21203/rs.3.rs-1075362/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ee704015-710f-4f54-9622-19d832e86ac8","owner":[],"postedDate":"November 30th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":8804424,"name":"Molecular Genetics"},{"id":8804425,"name":"Molecular Biology"}],"tags":[],"updatedAt":"2022-01-13T12:34:47+00:00","versionOfRecord":[],"versionCreatedAt":"2021-11-30 17:45:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1075362","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1075362","identity":"rs-1075362","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}