The PCAF histone acetylase plays an important role in regulation of transcription, cell cycle progression, and differentiation in conjunction with p300/CBP. To investigate PCAF function at the molecular level in greater detail, we purified PCAF in its native state. PCAF is found in a complex with more than 20 associated polypeptides. Strikingly, some polypeptides associated with PCAF are identical to the TBP-associated factors (TAFs) which are subunits of TFIID. Furthermore, some polypeptides show significant sequence similarity to other TAFs. Taken together, these results lead to the conclusion that a histone octamer-like domain may be present within the PCAF complex, as previously demonstrated in the TFIID complex. Although the function of the histone octamer-like structure in the PCAF complex is unclear, it may replace the histone octamer after relaxation of nucleosomal structure by acetylation of the histone tails. Importantly, the histone-like domains in the PCAF complex lack regions corresponding to histone N-terminal tails. In this regard, if it replaces the histone octamer, the histone-like structure in the PCAF complex may play an architectural role in the maintenance of a transcriptionally active chromatin state regardless of histone deacetylase activity. The fact that PCAF is found in a complex with more that 20 associated polypeptides suggests that E1A, by competing with PCAF for p300/CBP interaction, perturbs access of the PCAF complex to promoters. Thus, subunits in the PCAF complex may be involved in cellular events mediated by PCAF, i.e. regulation of transcription, cell cycle progression, and differentiation.
