title: Chd2 interacts with H3.3 to determine myogenic cell fate.
abstract: Cell differentiation is mediated by lineage-determining transcription factors. We show that chromodomain helicase DNA-binding domain 2 (Chd2), a SNF2 chromatin remodelling enzyme family member, interacts with MyoD and myogenic gene regulatory sequences to specifically mark these loci via deposition of the histone variant H3.3 prior to cell differentiation. Directed and genome-wide analysis of endogenous H3.3 incorporation demonstrates that knockdown of Chd2 prevents H3.3 deposition at differentiation-dependent, but not housekeeping, genes and inhibits myogenic gene activation. The data indicate that MyoD determines cell fate and facilitates differentiation-dependent gene expression through Chd2-dependent deposition of H3.3 at myogenic loci prior to differentiation.
authors.affiliation: Department of Advanced Medical Initiatives, JST-CREST, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Harada
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Daijiro
authors.initials: D
authors.lastname: Konno
authors.forename: Jun
authors.initials: J
authors.lastname: Odawara
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yoshimi
authors.forename: Saori
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumamaru
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Saiwai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tsubota
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.forename: Taro
authors.initials: T
authors.lastname: Tachibana
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Imbalzano
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D056426:Genetic Loci; D006657:Histones / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development; D017570:MyoD Protein / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C514205:Chd2 protein, mouse; D004268:DNA-Binding Proteins; D006657:Histones; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein