The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains

EMBO J. 2011 May 27;30(13):2596-609. doi: 10.1038/emboj.2011.166.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / genetics
  • CHARGE Syndrome / genetics
  • Chromatin Assembly and Disassembly / genetics
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleosomes / metabolism
  • Organisms, Genetically Modified
  • Phylogeny
  • Point Mutation
  • Protein Binding / genetics
  • Protein Interaction Domains and Motifs* / genetics
  • Protein Interaction Domains and Motifs* / physiology
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Homology, Amino Acid

Substances

  • CHD1 protein, S cerevisiae
  • DNA-Binding Proteins
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins

Associated data

  • PDB/ID2XB0