Polycomb regulation is coupled to cell cycle transition in pluripotent stem cells
MetadataShow full item record
AuthorAsenjo, Helena G.; Gallardo, Amador; López Onieva, Lourdes; Tejada, Irene; Martorell Marugán, Jordi; Carmona-Sáez, P.; Landeira, David
American Association for the Advancement of Science
Asenjo, H. G., Gallardo, A., Lopez-Onieva, L., Tejada, I., Martorell-Marugan, J., Carmona-Saez, P., & Landeira, D. (2020). Polycomb regulation is coupled to cell cycle transition in pluripotent stem cells; 6 : eaay4768
SponsorshipThis study was supported by the Spanish Ministry of Economy and Competitiveness (SAF2013-40891-R and BFU2016-75233-P) and the Andalusian Regional Government (PC-0246-2017). D.L. is a Ramón y Cajal researcher of the Spanish Ministry of Economy and Competitiveness (RYC-2012-10019).
When self-renewing pluripotent cells receive a differentiation signal, ongoing cell duplication needs to be coordinated with entry into a differentiation program. Accordingly, transcriptional activation of lineage specifier genes and cell differentiation is confined to the G1 phase of the cell cycle by unknown mechanisms. We found that Polycomb repressive complex 2 (PRC2) subunits are differentially recruited to lineage specifier gene promoters across cell cycle in mouse embryonic stem cells (mESCs). Jarid2 and the catalytic subunit Ezh2 are markedly accumulated at target promoters during S and G2 phases, while the transcriptionally activating subunits EPOP and EloB are enriched during G1 phase. Fluctuations in the recruitment of PRC2 subunits promote changes in RNA synthesis and RNA polymerase II binding that are compromised in Jarid2 −/− mESCs. Overall, we show that differential recruitment of PRC2 subunits across cell cycle enables the establishment of a chromatin state that facilitates the induction of cell differentiation in G1 phase.