Although mechanisms by which RNA polymerase II initiates transcription from the repressive chromatin is not clear, transcription initiation factor TFIID must have access to the core promoter on the chromatin. TFIID is the only factor which can bind by itself to the core promoter among the members of the preinitiation complex, and it builds a platform for the preinitiation complex. TFIID is a large multisubunit complex, consisting of the TATA-box binding protein (TBP) and a number of tightly associated subunits (TAFs). We observed that the N-terminal regions of Drosophila TAF42 (dTAF42) and TAF62 (dTAF62) have sequence similarities with the C- terminal core regions of histones H3 and H4, respectively. The histone-homologous regions of dTAF42 and dTAF62 form a heteromeric complex. However, neither dTAF42 nor dTAF62 forms a homomeric complex, in agreement with a nucleosomal histone character. The X-ray crystal structure of the dTAF42/dTAF62 complex indicates that TFIID contains a structure closely resembling that of the (H3/H4)2 heteromeric core of the histone octamer. Moreover, yeast suppressor screening and biochemical analyses suggest that TFIID contains a histone octamer-like structure composed of two dimers of the histone H2B-like TAF attached to a tetramer of histone H3/H4-like TAFs. Adenovirus can perturb the cell cycle by binding to p300 and CBP, which regulate transcription of the different genes required as the cycle progresses. We determined that a novel cellular factor (P/CAF) having intrinsic histone acetylase activity is associated with p300/CBP and competes with E1A for access to it. E1A can disrupt the P/CAF-p300/CBP complex, and may exert many of its effects on normal cellular function by this route. Conversely, overexpression of P/CAF in cultured cells inhibits the cell cycle and counteracts the activities of E1A.