Centromere Positioning Orchestrates Telomere Bouquet Formation and the Initiation of Meiotic Differentiation

Centromere Positioning Orchestrates Telomere Bouquet Formation and the Initiation of Meiotic Differentiation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Centromere Positioning Orchestrates Telomere Bouquet Formation and the Initiation of Meiotic Differentiation Alberto Jiménez-Martín, Alberto Pineda-Santaella, Rebeca Martín-García, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4016673/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Jan, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet. Here, using Schizosaccharomyces pombe as a model system to elucidate telomere bouquet function, we reveal that centromeres, traditionally perceived as playing a passive role in the chromosomal reorganization necessary for bouquet assembly, play a key role in the initiation of telomere bouquet formation. We demonstrate that centromeres are capable to induce telomere mobilization, which is sufficient to trigger the first stages of bouquet assembly and the meiotic transcription program in mitotic cells. This discovery highlights the finely tuned control exerted over long-distance heterochromatic regions and underscores a pivotal step in the mechanism of eukaryotic telomere bouquet formation and meiotic transcriptional rewiring. Biological sciences/Cell biology/Chromosomes/Telomeres Biological sciences/Cell biology/Chromosomes/Centromeres Biological sciences/Cell biology/Cell division/Meiosis telomeres centromeres Rabl chromosome conformation meiosis telomere bouquet chromosome architecture meiotic program Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementarymovie1.avi Supplementary video 1 SIJimenezMartinetal2024O.pdf TableS1.docx TableS2.docx Cite Share Download PDF Status: Published Journal Publication published 20 Jan, 2025 Read the published version in Nature Communications → 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-4016673","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":283773303,"identity":"291c739f-abe2-486c-8fdd-bcad1eecc2a7","order_by":0,"name":"Alberto Jiménez-Martín","email":"","orcid":"https://orcid.org/0000-0001-7628-1273","institution":"Institute of Functional Biology and Genomics","correspondingAuthor":false,"prefix":"","firstName":"Alberto","middleName":"","lastName":"Jiménez-Martín","suffix":""},{"id":283773304,"identity":"6d40f6d2-8ddf-4499-a2dd-7fc5ea260090","order_by":1,"name":"Alberto Pineda-Santaella","email":"","orcid":"https://orcid.org/0000-0003-1156-8104","institution":"Institute of Functional Biology and Genomics","correspondingAuthor":false,"prefix":"","firstName":"Alberto","middleName":"","lastName":"Pineda-Santaella","suffix":""},{"id":283773305,"identity":"8e23b86e-8902-41ce-8dca-010d845f850c","order_by":2,"name":"Rebeca Martín-García","email":"","orcid":"","institution":"Instituto de Biología Funcional y Genómica","correspondingAuthor":false,"prefix":"","firstName":"Rebeca","middleName":"","lastName":"Martín-García","suffix":""},{"id":283773306,"identity":"eed19f3a-f0d0-4526-b808-2b308434c6ce","order_by":3,"name":"Daniel León-Periñán","email":"","orcid":"https://orcid.org/0000-0002-7970-0362","institution":"Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"León-Periñán","suffix":""},{"id":283773307,"identity":"dceb5beb-3633-46ca-bb4c-28ea59f552a9","order_by":4,"name":"Antonia Terrizzano","email":"","orcid":"","institution":"Curie Institute","correspondingAuthor":false,"prefix":"","firstName":"Antonia","middleName":"","lastName":"Terrizzano","suffix":""},{"id":283773308,"identity":"2de03560-1127-4747-9ff7-d5fcc9596e9a","order_by":5,"name":"Rafael Daga","email":"","orcid":"","institution":"Centro Andaluz de Biología del Desarrollo","correspondingAuthor":false,"prefix":"","firstName":"Rafael","middleName":"","lastName":"Daga","suffix":""},{"id":283773309,"identity":"5addb72a-ac02-409c-b442-c1e81b84e0e8","order_by":6,"name":"Sigurd Braun","email":"","orcid":"https://orcid.org/0000-0001-6399-8574","institution":"Justus-Liebig-University Giessen","correspondingAuthor":false,"prefix":"","firstName":"Sigurd","middleName":"","lastName":"Braun","suffix":""},{"id":283773302,"identity":"52f846f1-f51d-4f42-8a94-701f828f1ab4","order_by":7,"name":"Alfonso Fernández-Álvarez","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-7455-1425","institution":"Instituto de Biología Funcional y Genómica (CSIC/USAL)","correspondingAuthor":true,"prefix":"","firstName":"Alfonso","middleName":"","lastName":"Fernández-Álvarez","suffix":""}],"badges":[],"createdAt":"2024-03-05 11:10:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4016673/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4016673/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41467-025-56049-9","type":"published","date":"2025-01-20T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":53450944,"identity":"ebf0a96c-ec05-41bf-b947-3aa84a3c13fa","added_by":"auto","created_at":"2024-03-26 06:39:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1244388,"visible":true,"origin":"","legend":"\u003cp\u003eCentromere-SPB association regulates meiotic gene expression. (A) Schematic representation of the centromere-SPB interaction in fission yeast. (B) State of the interphase centromere (Mis6-GFP)-SPB (Sid4-mCherry) interaction in Rabl+ and Rabl– (sad1-2 csi1Δ) cells; scale bars, 2 μm). (C) Volcano plot depicting RNA-seq data from sad1-2 csi1Δ versus control cells. Genes significantly up- (red) or downregulated (blue) are highlighted (log2(fold change) \u0026gt; 0.5 or \u0026lt; -0.5 with p-value \u0026lt; 0.05 by the Wald test, as implemented within the DESeq2 framework), and the number in each group is indicated. Highlighted in bold are the name of the most significant meiotic upregulated genes from RNAseq data. (D) M (log ratio) and A (mean average) (MA) plot depicting RNA-seq data from sad1-2 csi1Δ versus control cells. Genes significantly up- (red) or downregulated (blue) are highlighted (log2(fold change) \u0026gt; 0.5 or \u0026lt; -0.5 compared to log2(mean expression)), and the number in each group is indicated. Highlighted the most significant upregulated meiotic genes. (E) Venn diagram depicting the comparison between RNA-seq data from sad1-2 csi1Δ versus control cells (log2(fold change) \u0026gt; 0.3 or \u0026lt; -0.3 with p-value \u0026lt; 0.05 by the Wald test, as implemented within the DESeq2 framework) and RNA-seq data from meiotic cells versus vegetative cells (from [78]). The p-value from binomial test analysis is shown. (F) Table of the most upregulated meiotic797 specific genes from previous RNA-seq data. Gene name, meiotic stage, fold change and p-value are shown. (G) Plot of reads-per-million (RPM)-normalized read density at the indicated loci. Individual signals for each biological replicate are shown in a lighter colour, and the average of these is shown in a darker colour. Blue, wt; red, sad1-2 csi1Δ. (H) RT-qPCR analysis of relevant meiotic-specific genes showing RNA levels relative to wt after normalization to act1+. For all quantitative PCR experiments, data are represented as mean ± SEM from 3 independent experiments; ns represents no significant differences, and the asterisks denote p-value \u0026lt; 0.05 (∗), p-value \u0026lt; 0.01 (∗∗) and p-value \u0026lt; 0.001 (∗∗∗) from two-tailed Student’s t-test analysis. (I) Quantification of meiosis progression when centromere-SPB association is compromised. Representative DIC (Differential Interference Contrast) images of the distinct types of cells quantified in meiosis progression and efficiency experiments: Vegetative cells, meiocytes, asci, and asci \u0026lt; 4 spores. Scale bar, 5 μm. The mean percentage of cells from four independent experiments is shown for each analysed meiotic stage over a period of 48 hours. At least 300 cells were quantified for each time point in every analysed strain in each biological replicate.\u003c/p\u003e","description":"","filename":"Figure1O.png","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/6a33cf07f15d5e7b39343128.png"},{"id":53450945,"identity":"89f4ebfd-02b6-41a2-af65-c84a9867cd71","added_by":"auto","created_at":"2024-03-26 06:39:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":580764,"visible":true,"origin":"","legend":"\u003cp\u003eCentromere-SPB interaction represses 814 proximal and distal subtelomeric regions. (A) S. pombe subtelomeric and telomeric regions of chromosomes I and II, showing the shelterin domain (pink triangle), heterochromatic domain (purple semicircle), and knob domain (light green semicircle). Length bar (Kb) from telomere tip to the end of the subtelomere is also depicted. (B) RT-qPCR analysis of proximal subtelomeric regions of chromosomes I and II showing RNA levels relative to wt after normalization to act1+. tlh1+ and tlh2+ are located on the left and right arms of chromosomes I and II, respectively, but share 100% identity. Chromosome location and the distance to the telomere are indicated above for each analysed locus. (C) RT-qPCR analysis in distal subtelomeric regions of chromosomes I and II, as in (B). Chromosome location and the distance to the telomere are indicated above for each analysed locus. For all quantitative experiments, data are represented as mean ± SEM from 3 or 4 independent experiments; ns represents no significant differences, and the asterisks denote p-value \u0026lt; 0.05 (∗), p-value \u0026lt; 0.01 (∗∗), p-value \u0026lt; 0.001 (∗∗∗), and p-value \u0026lt; 0.0001 (∗∗∗∗) from two-tailed Student’s t-test analysis. (D) Plot of reads-per-million (RPM)-normalized read density at the indicated loci. Individual signals for each biological replicate are shown in a lighter colour, and the average of these is shown in a darker colour. Blue, wt; red, sad1-2 csi1Δ.\u003c/p\u003e","description":"","filename":"Figure2O.png","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/53d5a5c741bd88ccc9c88a6d.png"},{"id":53450953,"identity":"19d4f74c-50f7-49e8-8454-af2581e759df","added_by":"auto","created_at":"2024-03-26 06:39:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1814189,"visible":true,"origin":"","legend":"\u003cp\u003eLoss of centromere-SPB interaction leads to telomere declustering but the telomeres remain associated with the nuclear envelope. (A) Representative pictures of two-colour live-cell imaging of control, sad1-2, csi1Δ and sad1-2 csi1Δ strains during interphase. The telomeric protein Taz1 is visualized in green (Taz1-GFP), while the NE is shown in magenta (Ish1-mRFP). Scale bars, 5 μm. Insets show a magnified nucleus (scale bars, 2 μm). (B) Quantification of cells with a distinct number of telomere (Taz1-GFP) foci in the indicated strains. Shown is the percentage for a population of n cells combined from two independent experiments; asterisks denote p-value \u0026lt; 0.05, and p-value \u0026lt; 0.0001 (∗∗∗∗) from χ2 test analysis. (C) Representative pictures of two-colour live-cell imaging of dcr1Δ, ago1Δ and lem2Δ strains during interphase as in (A). Scale bars, 5 μm. Insets show a magnified nucleus (scale bars, 2 μm). (D) Quantification of cells with a distinct number of telomere (Taz1-GFP) foci in the indicated strains. Shown is the percentage for a population of n cells of one representative experiment for dcr1Δ, ago1Δ and lem2Δ strains; asterisks denote p-value \u0026lt; 0.0001 (∗∗∗∗) from χ2 test analysis. (E) Zone designation (I-III) and distribution of telomeres within 15 confocal planes with representative pictures (shown at right) (see Materials and methods). The telomeres are visualized by Taz1-GFP (in green), and the NE is visualized by Ish1-mRFP (in magenta). Representative pictures of nuclei in each zone designation are shown (scale bars, 2 μm). (F) Representative 851 pictures of one confocal plane of two-colour live-cell imaging of control, sad1-2 csi1Δ and lem2Δ strains during interphase. Scale bars, 5 μm. Insets show a magnified nucleus for each picture (scale bars, 2 μm). (G) Quantification of telomeres (Taz1-GFP) distribution relative to the nuclear periphery, showing the percentage of telomeres for each nuclear zone for a population of n cells from one representative experiment; ns represents no significant differences, and asterisks denote p-value \u0026lt; 0.01 (∗∗) and p-value \u0026lt; 0.001 (∗∗∗) from χ2 test analysis.\u003c/p\u003e","description":"","filename":"Figure3O.png","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/92a5a6450a9271d0e5f6ee9f.png"},{"id":53450946,"identity":"7328a2aa-9c3d-4d3a-a6e4-c9e417d7c420","added_by":"auto","created_at":"2024-03-26 06:39:38","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":939632,"visible":true,"origin":"","legend":"\u003cp\u003eTethering the centromeres to the SPB in sad1-2 csi1Δ cells restores both telomere clustering and returns transcription levels of subtelomeric regions and meiotic genes to normal. (A) Schematic representation of the GFP-GBP system used to force an interaction between the LINC complex (Sad1-2-GBP) and centromeres (Ndc80-GFP). (B) Serial dilutions (5-fold) of normalized log-phase cultures of the different indicated strains were spotted onto YE4S plates (+DMSO) containing the specified amounts of MBC or TBZ and incubated at 32ºC for 48 h. (C) Representative pictures of three-colour live-cell imaging of control, sad1-2 csi1Δ and sad1-2-GBP csi1Δ strains during interphase. The centromeric protein Ndc80 is in green (Ndc80-GFP), telomeres are in magenta (Taz1-mCherry), and the SPB is in blue (Cut12-CFP). Scale bars, 5 μm. Insets show a magnified nucleus for each picture (scale bars, 2 μm). (D-G) RT-qPCR analysis of proximal and distal subtelomeric region, and most representative meiotic genes. Chromosome location and the distance to the telomere is indicated above for each analysed locus in subtelomeric regions. For all quantitative experiments, data are represented as mean ± SEM from 3 independent experiments; ns represents no significant differences, and the asterisks denote p-value \u0026lt; 0.05 (∗), p-value \u0026lt; 0.01 (∗∗), p-value \u0026lt; 0.001 (∗∗∗), and p-value \u0026lt; 0.0001 (∗∗∗∗) from two-tailed Student’s t-test analysis.\u003c/p\u003e","description":"","filename":"Figure4O.png","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/e1cc23366b381e898e272383.png"},{"id":53450952,"identity":"0bb04812-ff43-414f-b06a-0038bddb10b9","added_by":"auto","created_at":"2024-03-26 06:39:39","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1015706,"visible":true,"origin":"","legend":"\u003cp\u003eThe alteration of centromere positioning enables telomeres to accommodate the bouquet proteins Bqt1 and Bqt2. (A) Both Bqt1 and Bqt2 were ectopically expressed in mitotic cells (control, and sad1-2 csi1Δ settings), and we examined the localization of Taz1-mCherry (telomeres), Bqt1- GFP and Ppc89-CFP (SPB). Scale bar, 2 μm. Among the observed cells, telomeres exhibited multiple foci in sad1-2 csi1Δ, as previously characterized in Figure 3, which were found mostly in association with Bqt1-GFP. Moreover, a significant proportion of the Bqt1-GFP foci did not co-localize with the SPB in mutant conditions. These rvations were made 16 h after the induction 887 of Bqt1 and Bqt2 expression. (B-C) Quantification of the phenotypes observed in (A). n represents the total number of telomeres (B) or SPBs (C) quantified per genotype in 7 independent biological replicates. Fisher’s exact test was applied, p-value \u0026lt; 0.0001 (∗∗∗∗). (D) Western blot analysis of protein samples from interphase cells of each indicated strain. Labels to the left indicate the antibodies used to probe the blots. The data shown are from a single representative experiment out of two repeats, and quantifications from below are the average of the Rap1-HA signal relative to the tubulin control from two independent experiments. (E) Quantification of the Rap1 protein levels relative to tubulin, showing the mean of the Rap1-HA signal relative to the tubulin control in arbitrary units (A.U.) from two independent experiments with standard deviations. The asterisk denotes p-value \u0026lt; 0.05 (∗) from two-tailed Student’s t-test analysis. (F) Representative pictures of one confocal plane of two-colour live-cell imaging of control and sad1-2 csi1Δ strains during interphase. Each subtelomeric loci (A01, at 50.9 kb from the telomere, or A67, at 99.7 kb from the telomere) of chromosome I is coloured green by the lacO array system (lacI902 GFP), while the NE is in magenta (Ish1-mRFP). Scale bars, 5 μm. (G) Quantification of each subtelomeric loci (A01 or A67) of chromosome I (lacI-GFP) distribution relative to the nuclear periphery as in Figure 3G. Shown is the percentage of subtelomeric loci for each nuclear zone for a population of n cells from one representative experiment; ns represents no significant differences, and the asterisks denote p-value \u0026lt; 0.01 (∗∗) and p-value \u0026lt; 0.0001 (∗∗∗∗) from χ2 test analysis.\u003c/p\u003e","description":"","filename":"Figure5O.png","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/203dbad3bde191570f06d36f.png"},{"id":53451619,"identity":"2515da7c-258a-43d8-a56e-a1ccaeacb472","added_by":"auto","created_at":"2024-03-26 06:47:39","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1016785,"visible":true,"origin":"","legend":"\u003cp\u003eThe outer kinetochore disassembles upon bouquet formation in diploid meiotic prophase. (A-B) Frames from time-lapse experiment of meiotic diploid cells expressing endogenously tagged Ndc80-GFP and Taz1-mCherry. Bouquet formation is referred to as time = 0. Scale bars, 5 μm. (C) Quantification of Ndc80-GFP intensity throughout the experiment as depicted in panels (A) and (B), with each colour representing the behaviour of 9 independent cells. (D) Working model for telomere bouquet formation upon meiotic entry: i) During mitotic interphase, fission yeast cells display a conserved Rabl chromosome configuration. In this conformation, centromeres are positioned beneath the SPB thanks to the interaction between the LINC complex (Kms1/2-Sad1) and the kinetochore complex (inner and outer kinetochore), with the aid of Csi1 and Lem2 proteins. Also, telomeres are located in the NE, at the opposite site of the nucleus, based on the interaction between the Bqt3-Bqt4 complex and the Rap1- Taz1 complex. ii) Nitrogen starvation conditions promote cells’ commitment to meiosis. At the beginning of meiotic prophase, centromeres decluster from the SPB due to the disappearance of the outer kinetochore, and telomeres also decluster between them, probably because of Rap1 protein degradation. 924 At this stage, telomere declustering facilitates their movement towards the SPB and the recruitment of bouquet proteins such as Bqt1 and Bqt2. iii) During prophase progression, centromere dissociation from the SPB is a prerequisite for telomere-SPB interaction, thanks to the recruitment of bouquet proteins (Bqt1 and Bqt2) to the LINC complex with the aid of the Bqt3-Bqt4 complex. iv) Bouquet formation occurs when centromeres are completely dissociated from the SPB. Then, telomeres are positioned beneath the SPB, based on the interaction between the LINC complex and the Rap1-Taz1 complex, which depends on the bouquet proteins (Bqt1 and Bqt2) and is aided by the Bqt3-Bqt4 complex.\u003c/p\u003e","description":"","filename":"Figure6O.png","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/14d2cdda49b27f6cd4ff2cc5.png"},{"id":74337833,"identity":"72edd9dc-582a-4485-bebb-db18fabd22ae","added_by":"auto","created_at":"2025-01-21 08:08:06","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3248269,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptAJMetal2024.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1_covered_2a5cf795-9b5a-4e1e-9053-b733863ced66.pdf"},{"id":53450947,"identity":"e304b828-241b-40f3-9aef-4df7c98b9ca9","added_by":"auto","created_at":"2024-03-26 06:39:38","extension":"avi","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17205972,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary video 1\u003c/p\u003e","description":"","filename":"Supplementarymovie1.avi","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/e8be3ed37267cbb9939ec5fb.avi"},{"id":53450949,"identity":"574e0673-facb-4e1b-88d3-dd9dd76a1e83","added_by":"auto","created_at":"2024-03-26 06:39:39","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":8747753,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"SIJimenezMartinetal2024O.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/c0909264497b3b26002778cd.pdf"},{"id":53450948,"identity":"cea54100-7d43-45dd-acc6-149729e5c3e7","added_by":"auto","created_at":"2024-03-26 06:39:38","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":29486,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/ac11aa267e0499d3603a5224.docx"},{"id":53450950,"identity":"c7b62e61-6bd0-470f-bccf-12cd5f909bcb","added_by":"auto","created_at":"2024-03-26 06:39:39","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":29045,"visible":true,"origin":"","legend":"","description":"","filename":"TableS2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4016673/v1/e4020d868f218d6760ea519d.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"\u003cp\u003eCentromere Positioning Orchestrates Telomere Bouquet Formation and the Initiation of Meiotic Differentiation\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"telomeres, centromeres, Rabl chromosome conformation, meiosis, telomere bouquet, chromosome architecture, meiotic program","lastPublishedDoi":"10.21203/rs.3.rs-4016673/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4016673/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAccurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet. Here, using \u003cem\u003eSchizosaccharomyces pombe\u003c/em\u003e as a model system to elucidate telomere bouquet function, we reveal that centromeres, traditionally perceived as playing a passive role in the chromosomal reorganization necessary for bouquet assembly, play a key role in the initiation of telomere bouquet formation. We demonstrate that centromeres are capable to induce telomere mobilization, which is sufficient to trigger the first stages of bouquet assembly and the meiotic transcription program in mitotic cells. This discovery highlights the finely tuned control exerted over long-distance heterochromatic regions and underscores a pivotal step in the mechanism of eukaryotic telomere bouquet formation and meiotic transcriptional rewiring.\u003c/p\u003e","manuscriptTitle":"Centromere Positioning Orchestrates Telomere Bouquet Formation and the Initiation of Meiotic Differentiation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-26 06:39:33","doi":"10.21203/rs.3.rs-4016673/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"bad21659-f28d-46a3-a1cd-9c1a60e32dee","owner":[],"postedDate":"March 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":29885346,"name":"Biological sciences/Cell biology/Chromosomes/Telomeres"},{"id":29885347,"name":"Biological sciences/Cell biology/Chromosomes/Centromeres"},{"id":29885348,"name":"Biological sciences/Cell biology/Cell division/Meiosis"}],"tags":[],"updatedAt":"2025-01-21T08:07:50+00:00","versionOfRecord":{"articleIdentity":"rs-4016673","link":"https://doi.org/10.1038/s41467-025-56049-9","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2025-01-20 05:00:00","publishedOnDateReadable":"January 20th, 2025"},"versionCreatedAt":"2024-03-26 06:39:33","video":"","vorDoi":"10.1038/s41467-025-56049-9","vorDoiUrl":"https://doi.org/10.1038/s41467-025-56049-9","workflowStages":[]},"version":"v1","identity":"rs-4016673","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4016673","identity":"rs-4016673","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}