title: The PHD and chromo domains regulate the ATPase activity of the human chromatin remodeler CHD4.
abstract: The NuRD (nucleosome remodeling and deacetylase) complex serves as a crucial epigenetic regulator of cell differentiation, proliferation, and hematopoietic development by coupling the deacetylation and demethylation of histones, nucleosome mobilization, and the recruitment of transcription factors. The core nucleosome remodeling function of the mammalian NuRD complex is executed by the helicase-domain-containing ATPase CHD4 (Mi-2β) subunit, which also contains N-terminal plant homeodomain (PHD) and chromo domains. The mode of regulation of chromatin remodeling by CHD4 is not well understood, nor is the role of its PHD and chromo domains. Here, we use small-angle X-ray scattering, nucleosome binding ATPase and remodeling assays, limited proteolysis, cross-linking, and tandem mass spectrometry to propose a three-dimensional structural model describing the overall shape and domain interactions of CHD4 and discuss the relevance of these for regulating the remodeling of chromatin by the NuRD complex.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
authors.forename: Aleksandra A
authors.initials: AA
authors.lastname: Watson
authors.forename: Pravin
authors.initials: P
authors.lastname: Mahajan
authors.forename: Haydyn D T
authors.initials: HD
authors.lastname: Mertens
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Deery
authors.forename: Wenchao
authors.initials: W
authors.lastname: Zhang
authors.forename: Peter
authors.initials: P
authors.lastname: Pham
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Du
authors.forename: Till
authors.initials: T
authors.lastname: Bartke
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Christian
authors.initials: C
authors.lastname: Edlich
authors.forename: Georgina
authors.initials: G
authors.lastname: Berridge
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Burgess-Brown
authors.forename: Tony
authors.initials: T
authors.lastname: Kouzarides
authors.forename: Nicola
authors.initials: N
authors.lastname: Wiechens
authors.forename: Tom
authors.initials: T
authors.lastname: Owen-Hughes
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
authors.forename: Opher
authors.initials: O
authors.lastname: Gileadi
authors.forename: Ernest D
authors.initials: ED
authors.lastname: Laue
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001324:Autoantigens / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D059748:Proteolysis
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D002843:Chromatin; D009707:Nucleosomes; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases