Epstein-Barr virus nuclear protein 2 interacts with p300, CBP, and PCAF histone acetyltransferases in activation of the LMP1 promoter

The Epstein-Barr virus (EBV) nuclear protein 2 (EBNA2) and herpes simplex v irion protein 16 (VP16) acidic domains that mediate transcriptional activat ion now are found to have affinity for p300, CBP, and PCAF histone acetyltr ansferases (HATs). Transcriptionally inactive point mutations in these doma ins lack affinity for p300, CBP. or PCAF, P300 and CBP copurify with the pr incipal HAT activities that bind to EBNA2 or VP16 acidic domains through ve locity sedimentation and anion-exchange chromatography. EBNA2 binds to both the N- and C-terminal domains of p300 and coimmune-precipitates from trans fected 293T cells with p300, In EBV-infected Akata Burkitt's tumor cells th at do not express the EBV encoded oncoproteins EBNA2 or LMP1, p300 expressi on enhances the ability of EBNA2 to up-regulate LMP? expression. Through it s intrinsic: HAT activity, PCAF can further potentiate the p300 effect. In 293 T cells, P300 and CBP (but not PCAF) can also coactivate transcription mediated by the EBNA2 or VP16 acidic domains and HAT-negative mutants of p3 00 have partial activity. Thus, the EBNA2 and VP16 acidic domains can utili ze the intrinsic HAT or scaffolding properties of p300 to activate transcri ption.