NuA4TIP60

NuA4TIP60 is a conserved chromatin-modifying histone acetyltransferase complex that combines features of the yeast NuA4 complex and the mammalian TIP60 complex. It is present in eukaryotes and functions as a multi-subunit enzyme responsible for acetylating histones and regulating chromatin structure. In yeast, the catalytic core is Esa1, whereas in humans the catalytic subunit is Tip60 (also known as KAT5). The complex includes a set of regulatory and scaffolding subunits that aid in assembly, chromatin targeting, and functional coupling to transcription and DNA repair.

Biochemically, NuA4TIP60 possesses histone acetyltransferase activity and primarily targets histones H4, and to a lesser extent other histones, at multiple lysine residues. This acetylation event is associated with open chromatin and transcriptional activation, and it also participates in signaling pathways that respond to DNA damage.

Subunit composition varies across species but generally features a catalytic subunit (Esa1 in yeast or Tip60/KAT5 in humans) together with regulatory and adaptor proteins that mediate recruitment to promoters and to sites of DNA damage. In humans, the complex interfaces with other chromatin regulators and coactivators, including partner proteins involved in chromatin remodeling and damage response. The precise arrangement and contribution of individual subunits support both transcriptional regulation and genome maintenance functions.

Functions and significance: NuA4TIP60 plays a dual role in transcription and DNA damage repair. By acetylating histones, it promotes an open chromatin state conducive to transcription. In the DNA damage response, its activity facilitates the recruitment of repair factors to breaks and influences signaling pathways that maintain genome integrity. The complex is thus a key link between chromatin modification and cellular responses to genomic stress.