Developmental control of polycomb subunit composition by GATA factors mediates a switch to non-canonical functions

Jian Xu, Zhen Shao, Dan Li, Huafeng Xie, Woojin Kim, Jialiang Huang, Jordan E. Taylor, Luca Pinello, Kimberly Glass, Jacob D. Jaffe, Guo Cheng Yuan, Stuart H. Orkin

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Polycomb repressive complex 2 (PRC2) plays crucial roles in transcriptional regulation and stem cell development. However, the context-specific functions associated with alternative subunits remain largely unexplored. Here we show that the related enzymatic subunits EZH1 and EZH2 undergo an expression switch during blood cell development. An erythroid-specific enhancer mediates transcriptional activation of EZH1, and a switch from GATA2 to GATA1 controls the developmental EZH1/2 switch by differential association with EZH1 enhancers. We further examine the invivo stoichiometry of the PRC2 complexes by quantitative proteomics and reveal the existence ofan EZH1-SUZ12 subcomplex lacking EED. EZH1 together with SUZ12 form a non-canonical PRC2 complex, occupy active chromatin, and positively regulate gene expression. Loss of EZH2 expression leads to repositioning of EZH1 to EZH2 targets. Thus, the lineage- and developmental stage-specific regulation of PRC2 subunit composition leads to a switch from canonical silencing to non-canonical functions during blood stem cell specification.

Original languageEnglish (US)
Pages (from-to)304-316
Number of pages13
JournalMolecular cell
Volume57
Issue number2
DOIs
StatePublished - Jan 22 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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