PHD (plant homeodomain) zinc fingers are structurally conserved modules found in proteins that modify chromatin as well as mediate molecular interactions in gene transcription. The original discovery of their role in gene transcription is attributed to the recognition of lysine-methylated histone H3. Recent studies show that PHD fingers have a sophisticated histone sequence reading capacity that is modulated by the interplay between different histone modifications. These studies underscore the functional versatility of PHD fingers as epigenome readers that control gene expression through molecular recruitment of multiprotein complexes of chromatin regulators and transcription factors. Moreover, they reinforce the concept that evolutionary changes in amino acids surrounding ligand binding sites on a conserved structural fold impart great functional diversity upon this family of proteins.
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