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Structures and Binding Specificities of the human CHD family double chromodomains
Author(s) -
Wiggins Kimberly,
Kim Daesung,
Khorasanizadeh Sepideh
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.705.2
Subject(s) - chromodomain , chromatin , helicase , histone , epigenetics , dna , biology , genetics , gene , computational biology , chemistry , rna
CHD (Chromo Helicase DNA‐binding) polypeptides contain a pair of tandem chromodomains adjacent to a SNF2‐type helicase domain. Nine distinct genes in human encode CHD proteins all implicated in chromatin remodelling. Our group has established the structure and specificity of CHD1 which binds to a lysine 4 methylated histone H3 tail. Sequences in the CHD chromodomain regions suggest the family has expanded to acquire novel target selectivity. We expect these differences contribute to distinct epigenetic signalling during differentiation. Therefore, we are elucidating the structures and functions of uncharacterized human CHD chromodomains. Using in‐vitro fluorescence binding assays, we have characterized the binding specificities of CHD4, CHD7 and CHD9 chromodomains. While CHD7 and CHD9 prefer interactions with methylated histone tails, CHD4 prefers binding to DNA. The molecular bases for specificity in these complexes are being investigated by Nuclear Magnetic Resonance Spectroscopy and X‐ray Crystallography. Structural determinants of peptide and DNA binding will provide the knowledge necessary to design point mutations that could be tested in tissue culture studies to further elucidate the role of chromodomains during differentiation. NIH NIGMS funding is acknowledged through a Ruth L. Kirschstein NRSA and RO1.