title: Roles of H3K27me2 and H3K27me3 Examined during Fate Specification of Embryonic Stem Cells.
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.
authors: 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.
authors: Aster H
authors: AH
authors: Juan
authors: 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.
authors: Stan
authors: S
authors: Wang
authors: 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.
authors: Kyung Dae
authors: KD
authors: Ko
authors: 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.
authors: Hossein
authors: H
authors: Zare
authors: 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.
authors: Pei-Fang
authors: PF
authors: Tsai
authors: 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.
authors: Xuesong
authors: X
authors: Feng
authors: 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.
authors: Karinna O
authors: KO
authors: Vivanco
authors: 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.
authors: Anthony M
authors: AM
authors: Ascoli
authors: 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.
authors: Gustavo
authors: G
authors: Gutierrez-Cruz
authors: Genomics and Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Jordan
authors: J
authors: Krebs
authors: Epigenetics Program, Department of Biochemistry and Biophysics, Perlman School of Medicine, University of Pennsylvania, Philadelphia 19104 PA, USA.
authors: Simone
authors: S
authors: Sidoli
authors: Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Adam L
authors: AL
authors: Knight
authors: 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.
authors: Roger A
authors: RA
authors: Pedersen
authors: Epigenetics Program, Department of Biochemistry and Biophysics, Perlman School of Medicine, University of Pennsylvania, Philadelphia 19104 PA, USA.
authors: Benjamin A
authors: BA
authors: Garcia
authors: Genomics and Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Rafael
authors: R
authors: Casellas
authors: iPSC Core Facility, Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Jizhong
authors: J
authors: Zou
authors: 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.
authors: Vittorio
authors: V
authors: Sartorelli
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D016678:Genome; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D017393:RNA Editing; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D000069896:Transcription Activator-Like Effector Nucleases / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D000069896:Transcription Activator-Like Effector Nucleases; D008239:Lysine
keywords: H3K27 methylation; embryonic stem cells; polycomb proteins