title: Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation.
abstract: Nucleosome occupancy is fundamental for establishing chromatin architecture. However, little is known about the relationship between nucleosome dynamics and initial cell lineage specification. Here, we determine the mechanisms that control global nucleosome dynamics during embryonic stem (ES) cell differentiation into endoderm. Both nucleosome depletion and de novo occupation occur during the differentiation process, with higher overall nucleosome density after differentiation. The variant histone H2A.Z and the winged helix transcription factor Foxa2 both act to regulate nucleosome depletion and gene activation, thus promoting ES cell differentiation, whereas DNA methylation promotes nucleosome occupation and suppresses gene expression. Nucleosome depletion during ES cell differentiation is dependent on Nap1l1-coupled SWI/SNF and INO80 chromatin remodeling complexes. Thus, both epigenetic and genetic regulators cooperate to control nucleosome dynamics during ES cell fate decisions.
authors.affiliation: Department of Genetics and Institute of Diabetes, Obesity and Metabolism, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Li
authors.forename: Paul
authors.initials: P
authors.lastname: Gadue
authors.forename: Kaifu
authors.initials: K
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.forename: Geetu
authors.initials: G
authors.lastname: Tuteja
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schug
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism*
chemical_list: C496503:Foxa2 protein, mouse; D006657:Histones; D009707:Nucleosomes; C077020:histone H2A.F-Z; D051542:Hepatocyte Nuclear Factor 3-beta