Polycomb-like 2 associates with PRC2 and regulates transcriptional networks during mouse embryonic stem cell self-renewal and differentiation

Cell Stem Cell. 2010 Feb 5;6(2):153-66. doi: 10.1016/j.stem.2009.12.014.

Abstract

Polycomb group (PcG) proteins are conserved epigenetic transcriptional repressors that control numerous developmental gene expression programs and have recently been implicated in modulating embryonic stem cell (ESC) fate. We identified the PcG protein PCL2 (polycomb-like 2) in a genome-wide screen for regulators of self-renewal and pluripotency and predicted that it would play an important role in mouse ESC-fate determination. Using multiple biochemical strategies, we provide evidence that PCL2 is a Polycomb Repressive Complex 2 (PRC2)-associated protein in mouse ESCs. Knockdown of Pcl2 in ESCs resulted in heightened self-renewal characteristics, defects in differentiation, and altered patterns of histone methylation. Integration of global gene expression and promoter occupancy analyses allowed us to identify PCL2 and PRC2 transcriptional targets and draft regulatory networks. We describe the role of PCL2 in both modulating transcription of ESC self-renewal genes in undifferentiated ESCs as well as developmental regulators during early commitment and differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Line
  • Cellular Reprogramming*
  • Down-Regulation
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Profiling
  • Gene Regulatory Networks*
  • Genome-Wide Association Study
  • Histones / metabolism
  • Methylation
  • Mice
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Polycomb Repressive Complex 2
  • Polycomb-Group Proteins
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • Histones
  • Mtf2 protein, mouse
  • Polycomb-Group Proteins
  • Repressor Proteins
  • Polycomb Repressive Complex 2

Associated data

  • GEO/GSE16364
  • GEO/GSE16526