Multiple TATA-Binding Factors Come Back Into Style

Abstract

What are the implications of multiple TFIIDs? It introduces even more complexity to the RNA polymerase II transcription apparatus, which already is thought to contain upwards of 50 proteins. The stock answer to the question of “Why so many proteins?” is that it provides multiple points of regulation and a combinatorial diversity that is necessary for the complicated genetic program involved in metazoan development and adaptation. That may be part of the explanation, and a few gene knockout experiments in mice will undoubtedly address that hypothesis. However, the yeast transcription machinery is very similar to and nearly as complicated as the mammalian or fly (although there is only one TBP in yeast), and it suggests that some of these TAFs have basic functions other than simply acting as targets for activator proteins.The Green and Struhl labs made the somewhat unsettling discovery that the loss of many TAFs in yeast did not result in a general loss of transcription (9xMoqtaderi, Z., Bai, Y., Poon, D., Weil, P.A., and Struhl, K. Nature. 1996; 383: 188–191CrossRef | PubMed | Scopus (230)See all References, 17xWalker, S.S., Reese, J.C., Apone, L.M., and Green, M.R. Nature. 1996; 383: 185–188CrossRef | PubMed | Scopus (200)See all References). Upon closer examination, it has become clear that there is a small subset of genes that show a strong dependence on yTAFII145 (11xShen, W.C. and Green, M.R. Cell. 1997; 90: 615–624Abstract | Full Text | Full Text PDF | PubMed | Scopus (155)See all References, 18xWalker, S.S., Shen, W.C., Reese, J.C., Apone, L.M., and Green, M.R. Cell. 1997; 90: 607–614Abstract | Full Text | Full Text PDF | PubMed | Scopus (124)See all References). Interestingly, the TAF-requiring genes identified so far appear to fall in families, specifically G1- and B-type cyclins and the ribosomal protein genes. Strikingly, the dependence on TAFs is not conferred by the regulatory factors bound upstream in the promoter, but rather by sequence elements in the basal promoter. Also, it is interesting to note that loss of yTAFII145 causes some genes to increase their level of expression (Shen and Green 1997xShen, W.C. and Green, M.R. Cell. 1997; 90: 615–624Abstract | Full Text | Full Text PDF | PubMed | Scopus (155)See all ReferencesShen and Green 1997). Therefore, it is probably too simple to think of TAFs as one entity: each TFIID subunit may have different effects on different promoters. In some contexts, a single TAF might act as a coactivator for a specific regulatory protein. In others, it may function primarily as a basal transcription factor, exhibiting enzymatic activity or recognizing specific promoter sequences. In yet another promoter context, the same TAF might act as a transcriptional repressor.The observation that the requirement for a specific TAF can be dependent upon basal promoter sequences echoes back to the earlier analyses suggesting that all TATA elements are not equivalent. Along similar lines, studies of the factor requirements for different basal promoters have demonstrated that some promoters are less dependent upon the RNA polymerase II C-terminal domain (Thompson et al. 1989xThompson, N.E., Steinberg, T.H., Aronson, D.B., and Burgess, R.R. J. Biol. Chem. 1989; 264: 11511–11520PubMedSee all ReferencesThompson et al. 1989) or TFIIE and/or TFIIH (Parvin et al. 1992xParvin, J.D., Timmers, H.T., and Sharp, P.A. Cell. 1992; 68: 1135–1144Abstract | Full Text PDF | PubMed | Scopus (61)See all ReferencesParvin et al. 1992). Therefore, the concept that basal promoters are generic and interchangeable is clearly an oversimplification. It will be extremely interesting to discover the molecular basis for TAF selectivity and to determine whether individual TAFs are required for unique sets of promoters. The recent advances in genomics should make this type of analysis feasible. Taken to its extreme, this line of thinking leads to the questions of whether every promoter makes a unique set of contacts with TFIID and the other basal transcription factors and whether these specific interactions contribute to the unique expression patterns of individual genes.