Initially TBP was thought to be a universal transcription factor. However, other TBP-related proteins have been identified, and organisms appear to have more than one type of TBP present in addition to the numerous TAF proteins. Multi-cellular organisms have evolved cell-type specific components of the general transcription apparatus to enable tissue-specific and gene-selective transcription. Some of these TBPs are spatially and temporally regulated, such as with TRF1 in Drosophila, which is expressed in embryos, the adult nervous system and in male germ cells, and which has a role in both Pol II and Pol III transcription. Therefore, TRF1 may have diversified from the more ubiquitous TBP to direct tissue-specific and possibly gene-selective transcription.
Another functional homologue of TBP is TRF2 present in many metazoan organisms. Link TRF1, TRF2 can bind to both TFIIA and TFIIB. TRF2 appears to be required for the transcription of certain key developmental genes.
Therefore, the diversity of TBP and TAF proteins allows cells to from multiple promoter recognition complexes that can be spatially or temporally regulated, as well as being gene selective.
Both positive and negative cofactors can interact with components of the general transcription machinery. One such general negative cofactor is NC2 (negative cofactor 2), whose a and b subunits are related in sequence to histones H2A and H2B, respectively. NC2 heterodimers can block the assembly of the pre-initiation complex through its ability to recognize the TBP-promoter complex and inhibit the incorporation of TFIIB and the positive cofactor TFIIA. In this way, NC2 converts the TBP-promoter complex into an inactive state. Another such negative cofactor is NOT. The strength of gene expression might depend in part upon the competition between the TBP inhibitors and the RNA polymerase holoenzyme for access to the TBP-promoter complex.