Regulation of histone acetyltransferases p300 and PCAF by the bHLH proteintwist and adenoviral oncoprotein E1A

Histone acetyltransferases (HAT) play a critical role in transcriptional co ntrol by relieving repressive effects of chromatin, and yet how HATs themse lves are regulated remains largely unknown. Here, it is shown that Twist di rectly binds two independent HAT domains of acetyltransferases, p300 and p3 00/CBP-associated factor (PCAF), and directly regulates their HAT activitie s. The N terminus of Twist is a primary domain interacting with both acetyl transferases, and the same domain is required for inhibition of p300-depend ent transcription by Twist. Adenovirus E1A protein mimics the effects of Tw ist by inhibiting the HAT activities of p300 and PCAF. These findings estab lish a cogent argument for considering the HAT domains as a direct target f or acetyltransferase regulation by both a cellular transcription factor and a viral oncoprotein.