The structural insight into the biological role of PHD fingers

Abstract

Covalent modifications of histone tails and protein domains 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 transcriptional regulators and chromatin‐associating complexes, however the overall biological role of this module 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 characterize the binding specificity of the PHD finger family using a set of biochemical, crystallographic and spectroscopic approaches. We compare the crystal structures of the H3K4me3‐bound PHD fingers, identify the binding sites for methylated histone H3 tails by resonance perturbation analysis and mutagenesis, and measure the binding affinities by tryptophan fluorescence. Our results provide novel insight into the molecular mechanisms underlying the activity of the histone‐binding PHD fingers, and further our understanding on how the histone code is read.