PHD Fingers: Epigenetic Effectors and Potential Drug Targets

Structural bases of histone code interpretation by PHD fingers. The crystal structures of (A) H3K4me3-bound ING2 PHD and (B) unH3-bound BHC80 PHD. The binding pockets for Ala¹, Arg², and Lys⁴me3/Lys⁴ are colored blue, salmon, and purple, respectively. The detailed coordination of these residues is highlighted (dashed circles) for (C) BPTF PHD-H3K4me3 and (D) BHC80 PHD-unH3. E) The PHD finger fold is characterized by the canonical Cys4-His-Cys3 (C4HC3) sequence that coordinates two zinc ions and contributes to the typical two-stranded anti-parallel β sheet structure. F) The dichotomy of coordination of Arg² in the RAG2 PHD-H3K4me3 complex (left) and AIRE PHD-unH3 complex (right).