title: Chromatin dynamics and the role of G9a in gene regulation and enhancer silencing during early mouse development.
abstract: Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which is essential for embryonic development. Here we show that genome-wide accumulation of H3K9me2 is crucial for postimplantation development, and coincides with redistribution of enhancer of zeste homolog 2 (EZH2)-dependent histone H3 lysine 27 trimethylation (H3K27me3). Loss of G9a or EZH2 results in upregulation of distinct gene sets involved in cell cycle regulation, germline development and embryogenesis. Notably, the H3K9me2 modification extends to active enhancer elements where it promotes developmentally-linked gene silencing and directly marks promoters and gene bodies. This epigenetic mechanism is important for priming gene regulatory networks for critical cell fate decisions in rapidly proliferating postimplantation epiblast cells.
authors.affiliation: Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.|Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jan J
authors.identifier: http://orcid.org/0000-0001-9622-5658
authors.initials: JJ
authors.lastname: Zylicz
authors.affiliation: Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sabine
authors.initials: S
authors.lastname: Dietmann
authors.affiliation: Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Günesdogan
authors.affiliation: Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Hackett
authors.affiliation: Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Delphine
authors.initials: D
authors.lastname: Cougot
authors.affiliation: Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lee
authors.affiliation: Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: M Azim
authors.identifier: 0000-0002-8640-4318
authors.initials: MA
authors.lastname: Surani
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D047108:Embryonic Development; D000071221:Enhancer of Zeste Homolog 2 Protein; D018507:Gene Expression Regulation, Developmental; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D002843:Chromatin; D006657:Histones; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2
keywords: chromosomes; developmental biology; epiblast; epigenetics; genes; histone; mouse; post-implantation; primed pluripotency; stem cells