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

Aster H Juan; Stan Wang; Kyung Dae Ko; Hossein Zare; Pei-Fang Tsai; Xuesong Feng; Karinna O Vivanco; Anthony M Ascoli; Gustavo Gutierrez-Cruz; Jordan Krebs; Simone Sidoli; Adam L Knight; Roger A Pedersen; Benjamin A Garcia; Rafael Casellas; Jizhong Zou; Vittorio Sartorelli

doi:10.1016/j.celrep.2016.09.087

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

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

Authors

Aster H Juan¹, Stan Wang², Kyung Dae Ko³, Hossein Zare³, Pei-Fang Tsai³, Xuesong Feng³, Karinna O Vivanco⁴, Anthony M Ascoli³, Gustavo Gutierrez-Cruz³, Jordan Krebs⁵, Simone Sidoli⁶, Adam L Knight⁷, Roger A Pedersen⁸, Benjamin A Garcia⁶, Rafael Casellas⁵, Jizhong Zou⁹, Vittorio Sartorelli¹⁰

Affiliations

¹ Laboratory 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.
² Laboratory 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.
³ Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Laboratory 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.
⁵ Genomics and Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Epigenetics Program, Department of Biochemistry and Biophysics, Perlman School of Medicine, University of Pennsylvania, Philadelphia 19104 PA, USA.
⁷ Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
⁸ Department 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.
⁹ iPSC Core Facility, Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁰ Laboratory 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.

Published by Elsevier Inc.

Publication types

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

MeSH terms

Animals
Cell Differentiation / genetics
Cell Lineage*
Embryoid Bodies / cytology
Embryoid Bodies / metabolism
Enhancer of Zeste Homolog 2 Protein / metabolism
Gene Expression Regulation
Genome
Histones / metabolism*
Lysine / metabolism*
Methylation
Mice
Mouse Embryonic Stem Cells / cytology*
Mouse Embryonic Stem Cells / metabolism*
Neurons / cytology
RNA Editing
Regulatory Sequences, Nucleic Acid / genetics
Transcription Activator-Like Effector Nucleases / metabolism
Transcription, Genetic

Substances

Histones
Enhancer of Zeste Homolog 2 Protein
Ezh2 protein, mouse
Transcription Activator-Like Effector Nucleases
Lysine

Abstract

Publication types

MeSH terms

Substances

Grants and funding