title: CHD4 Is a Peripheral Component of the Nucleosome Remodeling and Deacetylase Complex.
abstract: Chromatin remodeling enzymes act to dynamically regulate gene accessibility. In many cases, these enzymes function as large multicomponent complexes that in general comprise a central ATP-dependent Snf2 family helicase that is decorated with a variable number of regulatory subunits. The nucleosome remodeling and deacetylase (NuRD) complex, which is essential for normal development in higher organisms, is one such macromolecular machine. The NuRD complex comprises ∼10 subunits, including the histone deacetylases 1 and 2 (HDAC1 and HDAC2), and is defined by the presence of a CHD family remodeling enzyme, most commonly CHD4 (chromodomain helicase DNA-binding protein 4). The existing paradigm holds that CHD4 acts as the central hub upon which the complex is built. We show here that this paradigm does not, in fact, hold and that CHD4 is a peripheral component of the NuRD complex. A complex lacking CHD4 that has HDAC activity can exist as a stable species. The addition of recombinant CHD4 to this nucleosome deacetylase complex reconstitutes a NuRD complex with nucleosome remodeling activity. These data contribute to our understanding of the architecture of the NuRD complex.
authors.affiliation: From the School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia and.
authors.forename: Jason K K
authors.initials: JK
authors.lastname: Low
authors.affiliation: From the School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia and.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Webb
authors.affiliation: From the School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia and.
authors.forename: Ana P G
authors.initials: AP
authors.lastname: Silva
authors.affiliation: From the School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia and.
authors.forename: Hinnerk
authors.initials: H
authors.lastname: Saathoff
authors.affiliation: the Department of Genome Sciences, John Curtin School of Medical Research, Australian National University, Acton, Australian Capital Territory 2601, Australia.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Ryan
authors.affiliation: From the School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia and.
authors.forename: Mario
authors.initials: M
authors.lastname: Torrado
authors.affiliation: From the School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia and.
authors.forename: Mattias
authors.initials: M
authors.lastname: Brofelth
authors.affiliation: From the School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia and.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Parker
authors.affiliation: From the School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia and n.shepherd@imb.uq.edu.au.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Shepherd
authors.affiliation: From the School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia and joel.mackay@sydney.edu.au.
authors.forename: Joel P
authors.initials: JP
authors.lastname: Mackay
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D009707:Nucleosomes; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; C509277:Mi-2beta protein, mouse; D004265:DNA Helicases
keywords: CHD4; chromatin remodeling; gene regulation; nucleosome; nucleosome deacetylase complex (NuDe); nucleosome remodeling deacetylase (NuRD); structure-function