Histone acetyltransferase (HAT)

Histone acetyltransferases are a diverse family of enzymes that catalyze the transfer of acetyl groups from acetyl-CoA to lysine residues on histone tails, as well as on some non-histone proteins. This modification alters chromatin structure, typically resulting in increased transcriptional activity by making DNA more accessible to transcription factors. HATs exist as catalytic subunits within multisubunit complexes that guide substrate specificity and cellular localization. Key human HATs include HAT1, GCN5/KAT2A, p300, CBP, PCAF, and Tip60, among others, each contributing uniquely to cellular processes such as gene expression, DNA damage repair, cell cycle progression, and stem cell differentiation. Dysregulation or mutation of HATs is implicated in various diseases, most notably cancer, where altered acetylation patterns can drive oncogenic transcriptional programs. Ongoing drug development aims to modulate HAT function for therapeutic benefit, but clinical translation faces significant challenges related to enzyme selectivity and systemic safety.

Other names

HATHistone acetyltransferase 1 (HAT1)General control non-derepressible 5 (GCN5, KAT2A)p300/CBPPCAF (p300/CBP-associated factor)Tip60MOZ/MORF

Inhibition of enzymatic activity (blocking acetylation of lysine residues) Interference with cofactor (acetyl-CoA) binding Disruption of protein-protein interactions within multiprotein HAT complexes Selective targeting of specific HAT family members/substrates