 J Mol Biol. Author manuscript; available in PMC Jul 4, 2009.
Published in final edited form as: PMCID: PMC2576750
Inhibitor of growth 1 (ING1) is implicated in oncogenesis, DNA
damage repair and apoptosis. Mutations within the ING1 gene and
altered expression levels of ING1 are found in multiple human
cancers. Here, we show that both DNA repair and apoptotic
activities of ING1 require the interaction of the C-terminal
plant homeodomain (PHD) finger with trimethylated at Lys 4
histone H3 (H3K4me3). The ING1 PHD finger recognizes methylated
H3K4 but not other histone modifications as revealed by the
peptide microarrays. The molecular mechanism of the histone
recognition is elucidated based on a 2.1 Å resolution crystal
structure of the PHD-H3K4me3 complex. The K4me3 occupies a deep
hydrophobic pocket formed by the conserved Y212 and W235
residues that make cation–π contacts with the trimethylammonium
group. Both aromatic residues are essential in the H3K4me3
recognition, as substitution of these residues wi