Histone acetyltransferase 1 is a member of the GCN5 family of acetyltransferases that can acetylate Lys5 and Lys12 on newly generated histone H4, a process that is essential for mammalian development. HAT1 binds to the H4 gene promoter, where it facilitates the production and acetylation of new histones. This process is strongly dependent on glucose availability, suggesting HAT1 plays a role in nutrient sensing. HAT1 has also been shown to contribute to recovery from replication-based DNA damage by incorporating H4Lys5/Lys12 acetylated histones at the sites of double-stranded breaks. HAT1 can acetylate non-histone proteins as well, and has been shown to play a key role in NF-kB signaling by acetylating PLZF, which in turn forms a complex with p50 to limit the production of cytokines. HAT1 overexpression has also been implicated in many cancer types.
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