PHD Fingers: Epigenetic Effectors and Potential Drug Targets

Abstract

The plant homeodomain (PHD) finger is found in many chromatin-remodeling proteins. This small ~65-residue domain functions as an “effector” that binds specific epigenetic marks on histone tails, recruiting transcription factors and nucleosome-associated complexes to chromatin. Mutations in the PHD finger or deletion of this domain are linked to a number of human diseases, including cancer, mental retardation, and immunodeficiency. PHD finger–containing proteins may become valuable diagnostic markers and targets to prevent and treat these disorders. In this review, we highlight the progress recently made in understanding the functional significance of chromatin targeting by mammalian PHD fingers, detail the molecular mechanisms and structural features of “histone code” recognition, and discuss the therapeutic potential of PHD fingers.