EP300 Protein, Human (His)

p300 functions as a histone acetyltransferase that regulates transcription through chromatin remodeling. It acetylates all four core histones in nucleosomes, including histone H3 at Lys-122 (H3K122ac), Lys-18 (H3K18ac), and Lys-27 (H3K27ac), as well as histone H4 at Lys-5 (H4K5acme) and Lys-12 (H4K12acme), promoting transcriptional activation partly by enhancing nucleosome instability. Additionally, p300 acetylates non-histone targets such as ALX1, HDAC1, PRMT1, SIRT2, STAT3, and GLUL, modulating their functions. For example, acetylation of SIRT2 indirectly enhances p53/TP53 transcriptional activity, while STAT3 acetylation promotes dimerization and activation. p300 is involved in DNA damage response, heat shock response (HSR), circadian gene transcription, and the TGF-β signaling pathway. Beyond acetylation, p300 utilizes different acyl-CoA substrates (e.g., crotonyl-CoA, butyryl-CoA, 2-hydroxyisobutyryl-CoA, lactoyl-CoA, or propionyl-CoA) to mediate protein crotonylation, butyrylation, 2-hydroxyisobutyrylation, lactylation, or propionylation. During microbial infection, p300 is recruited by HIV-1 Tat protein to regulate its transactivating activity.