{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:15:01Z","timestamp":1788243301762,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ovarian follicle development plays a crucial role in mammalian fertility, which is primarily regulated by granulosa cell (GC) proliferation and cell cycle. Cell cycle dysregulation collectively might drive follicular atresia through GC dysfunction. However, the underlying molecular mechanisms remain largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The scRNA-seq and integrative analysis revealed that\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      was involved in cell cycle. Functional assays, including overexpression\/knockdown, flow cytometry, EdU, HE, and TUNEL, confirmed that\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      regulated cell cycle and follicular development\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      . CoIP showed that\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      bound CCNE1-CDK2-CDK1 to arrest G2\/M phase. Chromatin accessibility and CRISPR\/dCas9-TET1 demonstrated that DNA methylation modulated\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      transcription.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel regulator of cell cycle,\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      , was identified in Pig Genotype-Tissue Expression (PigGTEx). During GC proliferation, we found that\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      transcription was correlated with the distribution rate of G1 phase in GCs. PAFAH1B1 protein was confirmed to specifically bind to CCNE1-CDK2-CDK1 to arrest G2\/M phase. Notably,\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      appeared to hinder the development of follicles. Furthermore, the demethylation significantly promoted the transcription activity and chromatin accessibility of CpG island (\u22127\u00a0bp to +170\u00a0bp) of\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      . Taken together,\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      physically interacted with the CCNE1-CDK2-CDK1 complex to arrest G2\/M phase and inhibit the GCs proliferation and follicular development. Additionally, demethylation of CpG island significantly promoted the transcription of\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings not only advance understanding of cell proliferation and cycle regulation but also identify\n                      <jats:italic>PAFAH1B1<\/jats:italic>\n                      as a candidate gene for further investigation in follicular development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1919659","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:34:31Z","timestamp":1788240871000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PAFAH1B1 governs 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