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Mol Cell. 2015 Jan 22;57(2):304-316. doi: 10.1016/j.molcel.2014.12.009. Epub 2015 Jan 8.

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

Author information

1
Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
2
Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
4
Harvard College, Cambridge, MA 02138, USA.
5
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA 02115, USA.
6
The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
7
Howard Hughes Medical Institute, Boston, MA 02115, USA.
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Contributed equally

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 in vivo stoichiometry of the PRC2 complexes by quantitative proteomics and reveal the existence of an 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.

PMID:
25578878
PMCID:
PMC4305004
DOI:
10.1016/j.molcel.2014.12.009
[Indexed for MEDLINE]
Free PMC Article

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