TY - JOUR T1 - The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains A1 - Ryan,Daniel P. A1 - Sundaramoorthy,Ramasubramanian A1 - Martin,David A1 - Singh,Vijender A1 - Owen-Hughes,Tom AU - Ryan,Daniel P. AU - Sundaramoorthy,Ramasubramanian AU - Martin,David AU - Singh,Vijender AU - Owen-Hughes,Tom PY - 2011/7/6 Y1 - 2011/7/6 N2 -

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. The EMBO Journal (2011) 30, 2596-2609. doi:10.1038/emboj.2011.166; Published online 27 May 2011

AB -

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. The EMBO Journal (2011) 30, 2596-2609. doi:10.1038/emboj.2011.166; Published online 27 May 2011

KW - Chd1 KW - DNA binding KW - nucleosomes KW - SANT KW - SLIDE KW - SACCHAROMYCES-CEREVISIAE KW - PROTEIN-STRUCTURE KW - IN-VIVO KW - NUCLEOSOME KW - YEAST KW - ISWI KW - CHROMODOMAINS KW - COMPLEXES KW - ACF KW - TRANSCRIPTION UR - http://ukpmc.ac.uk/articles/PMC3155300 U2 - 10.1038/emboj.2011.166 DO - 10.1038/emboj.2011.166 M1 - Article JO - EMBO Journal JF - EMBO Journal SN - 0261-4189 IS - 13 VL - 30 SP - 2596 EP - 2609 ER -