Lysine acetyltransferase 6 family (KAT6)

The KAT6 family of histone acetyltransferases, primarily comprising KAT6A (MOZ) and KAT6B (MORF), are essential epigenetic regulators belonging to the MYST family [UniProt: Q92794, Q8WYB5]. These enzymes catalyze the acetylation of histone H3 at positions such as K9 and K23, which maintains an open chromatin state and promotes the transcription of genes critical for hematopoiesis and stem cell self-renewal [PMID: 30069049]. In oncology, KAT6A and KAT6B are frequently dysregulated through gene amplification or chromosomal translocations, particularly in acute myeloid leukemia and breast cancer, where they drive the expression of oncogenic cell cycle regulators like Cyclin D1 [PMID: 34644558]. Therapeutic strategies focus on highly selective small-molecule inhibitors that target the acetyl-CoA binding site of the KAT6 catalytic domain. These inhibitors have demonstrated the ability to induce permanent cell cycle arrest (senescence) in cancer cells, offering a promising non-genotoxic alternative to traditional chemotherapy [PMID: 30069049]. Clinical-stage candidates such as PF-07248144 are currently being investigated for their efficacy in patients with advanced solid tumors harboring KAT6A amplifications [NCT04606446].

Other names

MOZ/MORF familyMYST family histone acetyltransferases 3 and 4MYST3/MYST4Monocytic leukemia zinc finger protein family

Small-molecule inhibition of the MYST catalytic domain to prevent the transfer of an acetyl group from acetyl-CoA to lysine residues on histone H3, thereby inducing transcriptional reprogramming and cellular senescence [PMID: 30069049, PMID: 34644558].