Stimulation of CREB binding protein nucleosomal histone acetyltransferase activity by a class of transcriptional activators

The transcriptional coactivator CREB binding protein (CBP) possesses intrin sic histone acetyltransferase (HAT) activity that is important for gene reg ulation. CBP binds to and cooperates with numerous nuclear factors to stimu late transcription, but it is unclear if these factors modulate CBP HAT act ivity. Our previous work showed that CBP interacts with the Epstein-Barr vi rus-encoded basic region zipper (b-zip) protein, Zta, and augments its tran scriptional activity, Here we report that Zta strongly enhances CBP-mediate d acetylation of nucleosomal histones. Zta stimulated the HAT activity of C BP that had been partially purified or immunoprecipitated from mammalian ce lls as well as from sanity-purified, baculovirus expressed CBP. Stimulation of nucleosome acetylation required the CBP HAT domain, the Zta DNA binding and transcription activation domain, and nucleosomal DNA, In addition to Z ta, we found that two other b-zip proteins, NF-E2 and C/EBP alpha, strongly stimulated nucleosomal HAT activity. In contrast, several CBP-binding prot eins, including phospho-CREB, JUN/FOS, GATA-1, Pit-1, and EKLF, failed to s timulate HAT activity. These results demonstrate that a subset of transcrip tional activators enhance the nucleosome-directed HAT activity of CBP and s uggest that nuclear factors may regulate transcription by altering substrat e recognition and/or the enzymatic activity of chromatin modifying coactiva tors.