Transcription of protein-encoding genes in eukaryotes is regulated by various gene-specific transcriptional activators by interacting with RNA polymerase II transcription machinery. Transcription initiation factor TFIID is a potential target for activators and plays a central role in this communication. TFIID is a multisubunit complex containing a TATA box- binding factor (TBP) and associated polypeptides (TAFs). Importantly, while the native TFIID complex mediates both basal and activator-dependent transcription in reconstituted systems, TBP itself is competent only for basal transcription. Thus, TAFs are essential cofactors for regulated transcription. Recently, we have cloned most of TAFs with oligodeoxynucleotide probes based on partial amino acid sequences. The largest subunit, p230, shows significant sequence similarity with the product of human cell cycle gene (CCG1), also identified as the largest subunit of human TFIID complex, suggesting a specific role for a part of p230 in cell cycle regulated transcription. Moreover, p230 N-terminal portion interacts directly with TBP and inhibits both TATA box binding and basal transcription activities in the absence of other TAFs, suggesting that p230 negatively regulates promoter binding of TFIID complex. The second subunit, p110 interacts directly with p230 N-terminal portion which inhibits TBP function, suggesting a functional communication between p110 and TBP via p230 interactions. The third subunit, p85 contains eight of the WD-40 repeats found originally in the beta-subunit of G-proteins and more recently in other transcriptional regulatory factors. The WD-40 repeats in p85 may play a significant role in transducing signals by interactions with transcriptional regulators and/or other components of the basic transcriptional machinery. The p62 and p42 subunits have sequence similarities with H4 and H3 core histones, respectively, and interact tightly each other via histone-like domains. One interesting possibility is that p62/p42 interactions with DNA could facilitate the displacement of nucleosomal histones H3/H4 and/or maintain a compacted DNA structure near the transcription start site. Two small TAFs (p28, p22) are synthesized from the single gene by alternative splicing. Closely related TAFs are suggestive of TFIID heterogeneity.