GCN5PCAF

GCN5PCAF refers to the related histone acetyltransferase enzymes GCN5 and PCAF, encoded by the human KAT2A and KAT2B genes. They are the catalytic subunits of SAGA-type coactivator complexes and are conserved from yeast to humans. In mammalian cells, GCN5 and PCAF can function as mutually exclusive components within SAGA-like assemblies, supporting transcriptional activation through chromatin modification.

GCN5 and PCAF belong to the GNAT (Gcn5-related N-acetyltransferase) family and use acetyl-CoA to transfer acetyl groups to lysine residues on histone tails, particularly on histones H3 and H4. This histone acetylation reduces nucleosome compaction and promotes a more open chromatin state, facilitating gene expression. They also acetylate non-histone substrates, including certain transcription factors such as p53, influencing transcriptional regulation, DNA repair, and cell cycle progression.

Regulation of GCN5 and PCAF occurs at multiple levels, including expression of KAT2A and KAT2B, interactions with other SAGA subunits, and post-translational modifications that respond to cellular signaling. Their activity can be context-dependent, contributing to tissue-specific patterns of gene expression and developmental processes.

Dysregulation of GCN5PCAF has been associated with diseases, notably cancer, where altered acetylation patterns can affect gene expression and genomic stability. Research into selective modulators of GCN5 and PCAF aims to explore therapeutic potential for conditions involving epigenetic misregulation. Evolutionarily, GCN5 and PCAF arose from gene duplication and retain substantial similarity and overlapping functions, while also exhibiting distinct regulatory roles.