Modulation of the substrate preference of a MYST acetyltransferase by a scaffold protein.

ABSTRACT: The MYST family of lysine acetyltransferases are transcriptional regulators often dysregulated in cancer. In cells, MYST members form distinct multiprotein complexes that guide their histone substrate specificity, but how this selectivity is conferred is not fully understood. Here we interrogate a complex-mediated change in the substrate preference of the MYST member KAT6A, a target for cancer therapeutics. KAT6A forms a 4-protein complex with BRPF1, ING4/5, and MEAF6 to acetylate H3K23. However, additional substrates (H3K9, H3K14, and H3K27) have been proposed, and whether these residues are modified by KAT6A is unclear. We determined the histone substrate specificity of uncomplexed forms of KAT6A, including full-length KAT6A (KAT6A^FL) and the isolated acetyltransferase (MYST)

SUBMITTER: Sengupta RN 

PROVIDER: S-EPMC11946513 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature