TIP60s

TIP60s refers to a family of histone acetyltransferases led by TIP60, the human enzyme encoded by the KAT5 gene, and its orthologs in other species. They are members of the MYST family of histone acetyltransferases and function as catalytic subunits within larger multi-subunit chromatin-modifying complexes.

In humans, TIP60 is part of a NuA4-like, multi-subunit complex often described as the TIP60/p400 or NuA4-like complex. The complex cooperates with other subunits to acetylate histones, most notably histone H4 and the histone variant H2A.Z, promoting open chromatin and transcriptional activation. Beyond transcription, TIP60 complexes contribute to chromatin remodeling and the regulation of other chromatin-associated processes.

A key role of TIP60s is in the DNA damage response. They are recruited to sites of double-strand breaks and help activate DNA damage signaling pathways, including the activation of the ATM kinase through histone acetylation events. This activity facilitates access of repair factors to damaged DNA and influences the choice of repair pathways. TIP60s also participate in cell cycle control and apoptosis, linking chromatin state to cellular outcomes after stress.

Evolutionarily, TIP60s have orthologs across eukaryotes, with yeast Esa1 and related NuA4 components representing ancestral functions. Although the complex composition varies by organism, the core function as histone acetyltransferases that modify chromatin structure and regulate gene expression and genome stability is conserved.

Overall, TIP60s are central to chromatin regulation, transcriptional control, and the cellular response to DNA damage, functioning as catalytic cores within larger remodeling complexes.