The role of ubiquitous and cell specific coactivators in transcription regulation

The TATA-binding subunit (TBP) of natural TFIID and a number of other general initiation factors suffice for basal transcription by RNA polymerase II from most (e.g., TATA-containing) core promoters. In contrast, in cell free systems reconstituted with purified human factors, the function of gene-specific DNA-binding activators also requires various coactivators that include: (i) one or more of the other TFIID subunits (TAFs), which may also be involved in core promoter selectivity and activation, (ii) initiation factors (e.g., TFIIA) that may facilitate but are not essential for TBP-mediated basal transcription, (iii) one or more separable positive cofactors (PCI, PC2, PC3, PC4), purified from the general cofactor USA, that may act individually or in concert and (iv) in some cases, gene- or tissue-specific coactivators that show primary interactions with specific activators; examples include cell-specific coactivators involved in B cell-specific (OCA-B) and S phase-specific (OCA-S) trancription events through a common DNA binding activator (OCT-1), genespecific coactivators (TRAPs) that function with the thyroid hormone receptor, and coactivators (CBP, p300) with histone acetylase activities that function through a variety of activators such as nuclear hormone receptors and the tumor suppressor p53. Ongoing efforts have resulted in the further purification, cloning and characterization (structure, function and regulation) of various cofoctors and selected results relevant to variable cofactor requirements and activation mechanisms for different promoters will be discussed. This will include the demonstration of TAF-independent activator function in vitro in conjunction with human homologues of yeast holoenzyme-associated coactivators.