Polycomb regulation is coupled to cell cycle transition in pluripotent stem cells

Sci Adv. 2020 Mar 4;6(10):eaay4768. doi: 10.1126/sciadv.aay4768. eCollection 2020 Mar.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics*
  • Cell Differentiation
  • Cell Line, Transformed
  • Chromatin / chemistry*
  • Chromatin / metabolism
  • Elongin / genetics
  • Elongin / metabolism
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Gene Expression Regulation, Developmental*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism*
  • Polycomb Repressive Complex 2 / deficiency
  • Polycomb Repressive Complex 2 / genetics*
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Signal Transduction
  • Transcription, Genetic


  • Chromatin
  • Elob protein, mouse
  • Elongin
  • Jarid2 protein, mouse
  • Protein Subunits
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse
  • Polycomb Repressive Complex 2
  • RNA Polymerase II