title: H2A.Z facilitates access of active and repressive complexes to chromatin in embryonic stem cell self-renewal and differentiation.
abstract: Chromatin modifications have been implicated in the self-renewal and differentiation of embryonic stem cells (ESCs). However, the function of histone variant H2A.Z in ESCs remains unclear. We show that H2A.Z is highly enriched at promoters and enhancers and is required for both efficient self-renewal and differentiation of murine ESCs. H2A.Z deposition leads to an abnormal nucleosome structure, decreased nucleosome occupancy, and increased chromatin accessibility. In self-renewing ESCs, knockdown of H2A.Z compromises OCT4 binding to its target genes and leads to decreased binding of MLL complexes to active genes and of PRC2 complex to repressed genes. During differentiation of ESCs, inhibition of H2A.Z also compromises RA-induced RARα binding, activation of differentiation markers, and the repression of pluripotency genes. We propose that H2A.Z mediates such contrasting activities by acting as a general facilitator that generates access for a variety of complexes, both activating and repressive.
authors.affiliation: Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Gangqing
authors.initials: G
authors.lastname: Hu
authors.forename: Kairong
authors.initials: K
authors.lastname: Cui
authors.forename: Daniel
authors.initials: D
authors.lastname: Northrup
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.forename: Chaochen
authors.initials: C
authors.lastname: Wang
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Tang
authors.forename: Kai
authors.initials: K
authors.lastname: Ge
authors.forename: David
authors.initials: D
authors.lastname: Levens
authors.forename: Colyn
authors.initials: C
authors.lastname: Crane-Robinson
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002843:Chromatin / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000502:physiology
chemical_list: D002843:Chromatin; D006657:Histones; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse