P300CBPassociated

P300/CBP-associated factor, abbreviated PCAF, is a histone acetyltransferase in the GNAT family encoded by the human KAT2B gene. It is also known as KAT2B and is a nuclear coactivator that forms complexes with the transcriptional coactivators p300 and CBP to modulate gene expression.

PCAF functions primarily by acetylating histone tails, notably histones H3 and H4, which leads to a more open chromatin structure and enhanced transcription. In addition to histones, PCAF acetylates a variety of non-histone substrates, including transcription factors such as p53 and E2F1, thereby influencing their stability, DNA-binding activity, and transcriptional output. Through these activities, PCAF participates in diverse cellular processes, including cell cycle progression, DNA damage response, differentiation, and development.

Structurally, PCAF contains a histone acetyltransferase domain and typically features a bromodomain that recognizes acetylated lysines, facilitating recruitment to chromatin. Multiple isoforms can arise from alternative splicing, allowing tissue- and context-specific regulation of its activity.

Regulation of PCAF expression and activity is integrated with signaling pathways responsive to growth factors, stress, and differentiation cues. Aberrant PCAF function or expression has been linked to cancer and other diseases, reflecting its role as a key coactivator in transcriptional programs driven by p300/CBP and associated transcription factors. PCAF operates alongside related HATs such as GCN5 and CBP/p300 to coordinate chromatin modification and gene regulation.