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

Area of Science:

• Cell Biology
• Epigenetics
• Developmental Biology

Background:

• Pluripotent stem cells must coordinate cell division with differentiation.
• Transcriptional activation of differentiation genes is restricted to G1 phase.
• The underlying mechanisms for this cell cycle restriction are unknown.

Purpose of the Study:

• To investigate the role of Polycomb repressive complex 2 (PRC2) in cell cycle-regulated differentiation.
• To elucidate how PRC2 subunit recruitment varies across the cell cycle in mouse embryonic stem cells (mESCs).

Main Methods:

• Chromatin immunoprecipitation (ChIP) to assess PRC2 subunit recruitment to target gene promoters.
• Analysis of RNA synthesis and RNA polymerase II binding.
• Comparison of wild-type mESCs with Jarid2 knockout mESCs (Jarid2-/- mESCs).

Main Results:

• PRC2 subunits exhibit differential recruitment patterns across the cell cycle.
• Jarid2 and Ezh2 accumulate at promoters during S and G2 phases.
• EPOP and EloB are enriched during G1 phase, coinciding with differentiation.
• PRC2 subunit fluctuations impact RNA synthesis and RNA polymerase II binding.
• These dynamics are impaired in Jarid2-/- mESCs.

Conclusions:

• Differential recruitment of PRC2 subunits across the cell cycle is crucial for cell differentiation.
• This dynamic recruitment establishes a chromatin state permissive for G1-phase differentiation induction.
• PRC2 subunit fluctuations regulate gene expression timing during cell cycle progression.