title: The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains.
abstract: The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain. Here, we show the DNA-binding domain is required for Saccharomyces cerevisiae Chd1 to bind and remodel nucleosomes. The crystal structure of this domain reveals the presence of structural homology to SANT and SLIDE domains previously identified in ISWI remodelling enzymes. The presence of these domains in ISWI and Chd1 chromatin-remodelling enzymes may provide a means of efficiently harnessing the action of the Snf2-related ATPase domain for the purpose of nucleosome spacing and provide an explanation for partial redundancy between these proteins. Site directed mutagenesis was used to identify residues important for DNA binding and generate a model describing the interaction of this domain with DNA. Through inclusion of Chd1 sequences in homology searches SLIDE domains were identified in CHD6-9 proteins. Point mutations to conserved amino acids within the human CHD7 SLIDE domain have been identified in patients with CHARGE syndrome.
authors.affiliation: Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Ryan
authors.forename: Ramasubramanian
authors.initials: R
authors.lastname: Sundaramoorthy
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.forename: Vijender
authors.initials: V
authors.lastname: Singh
authors.forename: Tom
authors.initials: T
authors.lastname: Owen-Hughes
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D058747:CHARGE Syndrome / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D030781:Organisms, Genetically Modified; D010802:Phylogeny; D017354:Point Mutation; D011485:Protein Binding / Q000235:genetics; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: C489847:CHD1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins