Histone acetyltransferase KAT2A and Histone acetyltransferase KAT2B (KAT2A (GCN5), KAT2B (PCAF))

Histone acetyltransferase KAT2A and KAT2B are paralogous enzymes that catalyze acetylation of lysine residues on histone proteins, especially histone H3 at lysines 9 and 14, as well as various non-histone proteins[4][5][8]. KAT2A (GCN5, GCN5L2) and KAT2B (PCAF) play essential roles in the regulation of gene expression through epigenetic modification of chromatin, influencing processes such as DNA replication, DNA repair, transcription, cell cycle progression, cell death, and differentiation[2][4][5]. They are critical in stem cell maintenance, embryonic development, neural and immune regulation, and tissue renewal, with distinct and overlapping functions in different physiological and developmental contexts[1][2][6]. Double knockout or inhibition of both enzymes can result in loss of stem cell renewal, activation of innate immune signaling (such as IFN pathways), and lethal developmental phenotypes in animal models[1][6]. Their broad involvement in fundamental cellular processes highlights both their therapeutic potential and safety challenges as drug targets.

Other names

GCN5GCN5L2General control nonderepressible protein 5PCAFp300/CREB-binding protein-associated factor

Inhibitors block the lysine acetyltransferase activity, altering the acetylation of histone and non-histone proteins, thereby affecting gene expression and cellular function[7]. Inhibition can decrease H3K9 and H3K14 acetylation, disrupt chromatin structure, and interfere with gene transcription necessary for cell proliferation, differentiation, and survival[5][1][4].