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

Nat Commun. 2021 Sep 9;12(1):5341. doi: 10.1038/s41467-021-24894-z.

Abstract

Polycomb repressive complexes-1 and -2 (PRC1 and 2) silence developmental genes in a spatiotemporal manner during embryogenesis. How Polycomb group (PcG) proteins orchestrate down-regulation of target genes upon differentiation, however, remains elusive. Here, by differentiating embryonic stem cells into embryoid bodies, we reveal a crucial role for the PCGF1-containing variant PRC1 complex (PCGF1-PRC1) to mediate differentiation-associated down-regulation of a group of genes. Upon differentiation cues, transcription is down-regulated at these genes, in association with PCGF1-PRC1-mediated deposition of histone H2AK119 mono-ubiquitination (H2AK119ub1) and PRC2 recruitment. In the absence of PCGF1-PRC1, both H2AK119ub1 deposition and PRC2 recruitment are disrupted, leading to aberrant expression of target genes. PCGF1-PRC1 is, therefore, required for initiation and consolidation of PcG-mediated gene repression during differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Embryo, Mammalian
  • Embryoid Bodies / cytology
  • Embryoid Bodies / metabolism*
  • Gene Expression Regulation, Developmental*
  • Histones / genetics*
  • Histones / metabolism
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Mice, Transgenic
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism*
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Polycomb Repressive Complex 1 / genetics*
  • Polycomb Repressive Complex 1 / metabolism
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb Repressive Complex 2 / metabolism
  • Primary Cell Culture
  • SOXC Transcription Factors / genetics
  • SOXC Transcription Factors / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Ubiquitination

Substances

  • Histones
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Pcgf1 protein, mouse
  • Platelet-Derived Growth Factor
  • SOXC Transcription Factors
  • Sox4 protein, mouse
  • T-Box Domain Proteins
  • Tbx3 protein, mouse
  • Transcription Factors
  • grainy head-like 2 protein, mouse
  • platelet-derived growth factor A
  • Polycomb Repressive Complex 2
  • Polycomb Repressive Complex 1