Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target

Hiroki Sugishita1,2,3, Takashi Kondo1, Shinsuke Ito1

  • 1Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Nature Communications
|September 10, 2021
PubMed

Insights

The Polycomb repressive complex associated protein PCGF1-PRC1 is crucial for gene silencing during embryonic stem cell differentiation. It initiates repression by depositing histone H2AK119ub1 and recruiting PRC2, ensuring proper developmental gene regulation.

Area of Science:

  • Developmental biology
  • Epigenetics
  • Gene regulation

Background:

  • Polycomb repressive complexes (PRC1 and PRC2) are key epigenetic regulators of developmental gene expression during embryogenesis.
  • The precise mechanisms by which Polycomb group (PcG) proteins control target gene downregulation during cellular differentiation are not fully understood.

Purpose of the Study:

  • To elucidate the role of Polycomb group proteins in mediating gene silencing during embryonic stem cell differentiation.
  • To investigate the function of the PCGF1-containing PRC1 complex (PCGF1-PRC1) in differentiation-associated gene downregulation.

Main Methods:

  • Embryonic stem cells were differentiated into embryoid bodies to model early development.
  • Gene expression analysis was performed to identify target genes downregulated during differentiation.
  • Histone modification assays were used to detect H2AK119ub1 deposition.
  • Chromatin immunoprecipitation was employed to assess PRC2 recruitment.

Main Results:

  • PCGF1-PRC1 mediates the differentiation-associated downregulation of specific target genes.
  • PCGF1-PRC1 activity is associated with the deposition of histone H2AK119 mono-ubiquitination (H2AK119ub1) and recruitment of PRC2.
  • Loss of PCGF1-PRC1 function disrupts H2AK119ub1 deposition and PRC2 recruitment, leading to aberrant target gene expression.

Conclusions:

  • PCGF1-PRC1 plays a critical role in initiating and consolidating Polycomb-mediated gene repression during cellular differentiation.
  • This complex is essential for the proper spatiotemporal silencing of developmental genes required for embryogenesis.

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