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Structural characterization of histone‐binding PHD fingers
Author(s) -
Kutateladze Tatiana G,
Champagne Karen,
Pena Pedro,
Hom Robert,
Musselman Catherine,
Hung Tiffany,
Gozani Or
Publication year - 2008
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.22.1_supplement.599.5
Subject(s) - phd finger , histone code , histone , histone octamer , h3k4me3 , histone methylation , histone h1 , histone methyltransferase , epigenetics , chromatin , histone h2a , biology , histone h3 , genetics , microbiology and biotechnology , computational biology , chemistry , nucleosome , transcription factor , gene expression , gene , promoter , zinc finger , dna methylation
Post‐translational histone modifications and protein modules that bind these epigenetic marks are essential components of the chromatin remodeling and gene expression machinery. The PHD (plant homeodomain) finger is found in many chromatin‐associated complexes and transcription factors, however the biological function of this domain remains unclear. Recently, it was found that a subset of PHD fingers recognizes histone H3 tri‐methylated at lysine 4 (H3K4me3). In this study we aimed to characterize the determinants of the PHD finger's binding specificity toward modified and unmodified histone tails using X‐ray crystallography, NMR and fluorescence spectroscopic approaches. Here we report the crystal structures of ING1, ING4 and ING5 in complex with histone peptides, and identify residues important for the specific histone interactions. The histone binding sites were also mapped by resonance perturbation analysis and mutagenesis, and binding affinities were measured using tryptophan fluorescence. Together our results provide novel insights into the molecular mechanisms underlying the activity of the histone‐binding PHD fingers, and impart a greater understanding on how the histone code is read. Supported by NIH ( GM071424 and CA113472 to TGK).