Histone acetyltransferase KAT6A (MOZ) (KAT6A)

Histone acetyltransferase KAT6A (also known as MOZ or MYST3) is a chromatin-bound enzyme from the MYST family that catalyzes acetylation of lysine residues on histones H3 (at K9, K14, K23) and H4, as well as non-histone proteins like p53 and SMAD3, thereby regulating gene expression, transcriptional activation, and chromatin accessibility. It features structural domains including a winged helix for binding unmethylated CpG islands, double PHD fingers that recognize acetylated histones, and forms complexes with BRPF1, ING5, and EAF6 to enhance its activity at target loci such as HOX genes and PIK3CA promoter. KAT6A plays essential roles in hematopoietic stem cell development, cell proliferation, and cell cycle control, with knockout leading to embryonic lethality and reduced hematopoietic cells. Dysregulation drives oncogenesis, including acute myeloid leukemia via chromosomal translocations (e.g., KAT6A-TIF2 fusion) and glioblastoma through PI3K/AKT pathway upregulation via H3K23 acetylation and TRIM24 recruitment. Germline mutations cause neurodevelopmental disorders like Arima syndrome, featuring cognitive disability, microcephaly, and craniofacial abnormalities due to altered histone acetylation and p53 signaling. As a therapeutic target, KAT6A inhibitors are in development to block its acetyltransferase activity in cancers, though challenges include developmental toxicity risks.

Other names

MOZMYST3ZNF220MYST-3ZC2HC6ARUNXBP2MRD32

Histone H3K9, H3K14, H3K23 acetylation; Non-histone acetylation (e.g., p53 at K120/K382, SMAD3); Recruitment to unmethylated CpG islands via winged helix domain; Activation of PIK3CA transcription via H3K23ac and TRIM24