TBP-associated factors in the PCAF histone acetylase complex.

Abstract

PCAF (p300/CBP-associated factor) histone acetylasehas an important role in regulation of transcription, cellcycle progression, and differentiation in conjunction withp300/CBP. To investigate PCAF function at the molecular level in greater detail, we purified PCAF in its nativestate. PCAF is found in a complex with more than 20 associated polypeptides. Strikingly, some polypeptides associated with PCAF are identical to the TATA-box-binding polypeptide (TBP)-associated factors (TAFs) whichare subunits of TFIID. Furthermore, some polypeptidesshow significant sequence similarity to other TAFs.Taken together, these results lead to the conclusion that ahistone octamer-like domain may be present within thePCAF complex, as previously demonstrated in the TFIIDcomplex. Although the function of the histone octamerlike structure in the PCAF complex is unclear, it may replace the histone octamer after relaxation of nucleosomalstructure by acetylation of the histone tails. Importantly,the histone-like domains in the PCAF complex lack regions corresponding to histone amino-terminal tails. Inthis regard, if it replaces the histone octamer, the histonelike structure in the PCAF complex may have an architectural role in the maintenance of a transcriptionally active chromatin state regardless of histone deacetylaseactivity. The fact that PCAF is found in a complex withmore 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...