Background: The coactivator p300 acts as a transcriptional adaptor for many DNA-binding activators. The finding that p300 possesses intrinsic acetyltransferase activity which, by chemically modifying histone tails affects the nucleosomal environment and transcription, has greatly advanced our understanding of its function. Subsequent recent studies have shown that non-histone proteins are also acetylated. However, one central question which has remained unanswered is how the coactivator/acetyltransferase interacts with DNA-binding activators to modulate their actions.
Results: Here we have demonstrated physical and functional interaction between the acetyltransferase region of p300 and the DNA-binding domain (DBD) of the transcription factor Sp1. This interaction stimulates DNA binding by the DBD of Sp1, which is mediated primarily by physical interaction rather than acetylation, despite acetylation of the DBD of Sp1 by the acetyltransferase region of p300. Furthermore, DNA binding by the DBD of Sp1 inhibits both its association and acetylation by the acetyltransferase region of p300.
Conclusions: These findings suggest a new role for p300 in regulating promoter access by DNA-binding activators through multiple regulatory interactions.