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Cell Rep. 2016 Oct 25;17(5):1369-1382. doi: 10.1016/j.celrep.2016.09.087.

Roles of H3K27me2 and H3K27me3 Examined during Fate Specification of Embryonic Stem Cells.

Author information

  • 1Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: juana2@mail.nih.gov.
  • 2Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD 20892, USA; Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK.
  • 3Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD 20892, USA.
  • 4Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD 20892, USA; Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • 5Genomics and Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
  • 6Epigenetics Program, Department of Biochemistry and Biophysics, Perlman School of Medicine, University of Pennsylvania, Philadelphia 19104 PA, USA.
  • 7Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • 8Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK; The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.
  • 9iPSC Core Facility, Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • 10Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: sartorev@mail.nih.gov.

Abstract

The polycomb repressive complex 2 (PRC2) methylates lysine 27 of histone H3 (H3K27) through its catalytic subunit Ezh2. PRC2-mediated di- and tri-methylation (H3K27me2/H3K27me3) have been interchangeably associated with gene repression. However, it remains unclear whether these two degrees of H3K27 methylation have different functions. In this study, we have generated isogenic mouse embryonic stem cells (ESCs) with a modified H3K27me2/H3K27me3 ratio. Our findings document dynamic developmental control in the genomic distribution of H3K27me2 and H3K27me3 at regulatory regions in ESCs. They also reveal that modifying the ratio of H3K27me2 and H3K27me3 is sufficient for the acquisition and repression of defined cell lineage transcriptional programs and phenotypes and influences induction of the ESC ground state.

KEYWORDS:

H3K27 methylation; embryonic stem cells; polycomb proteins

PMID:
27783950
PMCID:
PMC5123747
DOI:
10.1016/j.celrep.2016.09.087
[PubMed - in process]
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