{"paper_id":"46e28d16-3f2a-4e46-afb7-a06c1da36849","body_text":"Conserved enhancer association of piRNAs and the implication in germ cell fate surveillance | 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 Research Article Conserved enhancer association of piRNAs and the implication in germ cell fate surveillance Pin-Jui Kung, Yi-Tzang Tsai, Gabrielle Marie Chungunco, Kai-Wei Chang, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6314689/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract The PIWI-piRNA pathway is crucial for protecting genomic integrity from derepressed transposon invasion in developing germ cells after genome-wide epigenetic erasure. Extensive mouse studies show that pre-pachytene piRNAs contribute to establishing the epigenetic landscape. However, little is known about human piRNAs during embryonic fetal germ cell development. In this study, we collected fetal testes of gestational week 12–22 abortuses from Taiwan and the USA, to investigate human piRNA profiles correlating to the time window of epigenetic landscape establishment. We identified numerous human piRNAs in second-trimester fetal testes that corresponded to small nucleolar RNAs. Additionally, a substantial proportion of human fetal testicular piRNAs mapped to super-enhancers and typical enhancers, a phenomenon conserved across mouse and chicken species. Notably, many of the pre-pachytene germline piRNAs mapped to enhancers active in various adult somatic lineages, implying they may regulate enhancer activities and safeguard germ cell identity by reducing aberrant expression of somatic genes. Germ Cells PIWI-interacting RNAs Post-Transcriptional Gene Silencing Enhancers Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 29 Oct, 2025 Reviews received at journal 18 Oct, 2025 Reviews received at journal 17 Oct, 2025 Reviewers agreed at journal 02 Oct, 2025 Reviewers agreed at journal 02 Oct, 2025 Reviewers invited by journal 23 Jun, 2025 Editor assigned by journal 31 Mar, 2025 Submission checks completed at journal 28 Mar, 2025 First submitted to journal 26 Mar, 2025 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. 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Extensive mouse studies show that pre-pachytene piRNAs contribute to establishing the epigenetic landscape. However, little is known about human piRNAs during embryonic fetal germ cell development. In this study, we collected fetal testes of gestational week 12\\u0026ndash;22 abortuses from Taiwan and the USA, to investigate human piRNA profiles correlating to the time window of epigenetic landscape establishment. We identified numerous human piRNAs in second-trimester fetal testes that corresponded to small nucleolar RNAs. Additionally, a substantial proportion of human fetal testicular piRNAs mapped to super-enhancers and typical enhancers, a phenomenon conserved across mouse and chicken species. 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