EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells

Mol Cell. 2016 Nov 17;64(4):645-658. doi: 10.1016/j.molcel.2016.10.018.

Abstract

The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding factor at the promoters of bivalent sites. Biochemical and genome-wide analyses show that Elongin BC is associated with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells. Elongin BC is recruited to chromatin by the PRC2-associated factor EPOP (Elongin BC and Polycomb Repressive Complex 2 Associated Protein, also termed C17orf96, esPRC2p48, E130012A19Rik), a protein expressed in the inner cell mass of the mouse blastocyst. Both EPOP and Elongin BC are required to maintain low levels of expression at PRC2 genomic targets. Our results indicate that keeping the balance between activating and repressive cues is a more general feature of chromatin in pluripotent stem cells than previously appreciated.

Keywords: Elongin; Polycomb; chromatin; epigenetics; gene regulation; pre-implantation development; stem cells; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Chromatin / chemistry
  • Chromatin / metabolism
  • DNA Polymerase II / genetics
  • DNA Polymerase II / metabolism
  • Elongin
  • Embryo Implantation
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental*
  • Histones / genetics
  • Histones / metabolism
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb Repressive Complex 2 / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Chromatin
  • E13 protein, mouse
  • Elongin
  • Histones
  • Nerve Tissue Proteins
  • Transcription Factors
  • Polycomb Repressive Complex 2
  • DNA Polymerase II