PCGF5 is required for neural differentiation of embryonic stem cells

Nat Commun. 2018 May 15;9(1):1463. doi: 10.1038/s41467-018-03781-0.


Polycomb repressive complex 1 (PRC1) is an important regulator of gene expression and development. PRC1 contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1), and has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway. PCGF5 loss-of-function impairs the reduction of H2AK119ub1 and H3K27me3 around neural specific genes and keeps them repressed. Our results suggest that PCGF5 might function as both a repressor for SMAD2/TGF-β signaling pathway and a facilitator for neural differentiation. Together, our findings reveal a critical context-specific function for PCGF5 in directing PRC1 to control cell fate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Line
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Histones / metabolism
  • Humans
  • Mice
  • Mouse Embryonic Stem Cells / cytology*
  • Mouse Embryonic Stem Cells / metabolism*
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Polycomb Repressive Complex 1 / metabolism
  • Polycomb-Group Proteins / deficiency
  • Polycomb-Group Proteins / genetics
  • Polycomb-Group Proteins / metabolism*
  • Signal Transduction
  • Smad2 Protein / metabolism
  • Transforming Growth Factor beta / metabolism
  • Ubiquitin-Protein Ligases / metabolism


  • Histones
  • Pcgf5 protein, mouse
  • Polycomb-Group Proteins
  • Smad2 Protein
  • Smad2 protein, mouse
  • Transforming Growth Factor beta
  • Polycomb Repressive Complex 1
  • Rnf2 protein, mouse
  • Ubiquitin-Protein Ligases