PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell pluripotency and somatic cell reprogramming

Stem Cells. 2011 Feb;29(2):229-40. doi: 10.1002/stem.578.

Abstract

Polycomb repressive complex two (PRC2) has been implicated in embryonic stem (ES) cell pluripotency; however, the mechanistic roles of this complex are unclear. It was assumed that ES cells contain PRC2 with the same subunit composition as that identified in HeLa cells and Drosophila embryos. Here, we report that PRC2 in mouse ES cells contains at least three additional subunits: JARID2, MTF2, and a novel protein denoted esPRC2p48. JARID2, MTF2, and esPRC2p48 are highly expressed in mouse ES cells compared to differentiated cells. Importantly, knockdowns of JARID2, MTF2, or esPRC2p48 alter the level of PRC2-mediated H3K27 methylation and result in the expression of differentiation-associated genes in ES cells. Interestingly, expression of JARID2, MTF2, and esPRC2p48 together, but not individually, enhances Oct4/Sox2/Klf4-mediated reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells, whereas knockdown or knockout of JARID2, MTF2, or esPRC2p48 significantly inhibits reprogramming. JARID2, MTF2, and esPRC2p48 modulate H3K27 methylation and facilitate repression of lineage-associated gene expression when transduced into MEFs, and synergistically stimulate the histone methyltransferase activity of PRC2 in vitro. Therefore, these studies identify JARID2, MTF2, and esPRC2p48 as important regulatory subunits of PRC2 in ES cells and reveal critical functions of these subunits in modulating PRC2's activity and gene expression both in ES cells and during somatic cell reprogramming.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Regulation, Developmental
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Octamer Transcription Factor-3 / metabolism
  • Pluripotent Stem Cells / metabolism*
  • Polycomb Repressive Complex 2
  • Polycomb-Group Proteins
  • Protein Binding
  • RNA, Small Interfering / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • SOXB1 Transcription Factors / metabolism

Substances

  • GKLF protein
  • Histones
  • Jarid2 protein, mouse
  • Kruppel-Like Transcription Factors
  • Mtf2 protein, mouse
  • Nerve Tissue Proteins
  • Octamer Transcription Factor-3
  • Polycomb-Group Proteins
  • Pou5f1 protein, mouse
  • RNA, Small Interfering
  • Repressor Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2