TAFs: Guilt by Association?

It is surprising that, in contrast to TBP, the TAFs are dispensable for transcriptional activation at many yeast promoters. Perhaps, in eukaryotes generally, TAFs are only required for transcription from a minority of promoters. We, however, suggest an alternate hypothesis: that the frequency with which TAFs are required for gene expression varies with genome complexity, much like the use of the splicing machinery.The basal pre-mRNA splicing machinery is highly conserved in eukaryotes but its overall use in gene expression varies with species. In humans, most genes have multiple introns and require the splicing machinery to be expressed properly. In S. cerevisiae, less than 5% of genes have introns—usually only one small intron—and hence most genes do not require the splicing machinery for proper expression (seeRymond and Rosbash 1992xSee all ReferencesRymond and Rosbash 1992). Thus, the basal splicing machinery has been conserved in both yeast and human cells and performs the same function in both species—removal of introns—but in human cells the splicing machinery is required for expression of a larger percentage of genes than in yeast.By analogy to the basal pre-mRNA splicing machinery, we suggest that TAFs are used more extensively in more complex organisms. Just as splicing is used more generally in humans to remove a larger number of introns, TAFs may be used more generally in humans than in yeast to direct transcription from a larger number of more complex enhancers/promoters and to respond to more numerous and varied activators. By exploiting the varied activities of TAFs, complex organisms may meet these added demands placed on the basal transcriptional machinery.The analogy to splicing can be extended even further: in pre-mRNA splicing, there is an elaboration of regulatory complexity through alternate splice-site utilization, which is used extensively in complex organisms but is apparently not conserved in yeast; accordingly, there is a family of proteins involved in alternate splice-site utilization—the SR protein family—that is not conserved in yeast. Analogous to the SR proteins, the metazoan dTAFII110/hTAFII130 and related cell-type-specific hTAFII105 may represent an elaboration of transcriptional regulatory complexity that facilitates complex patterns of metazoan–gene transcription (seeDikstein et al. 1996axDikstein, R, Zhou, S, and Tjian, R. Cell. 1996; 87: 137–146Abstract | Full Text | Full Text PDF | PubMed | Scopus (151)See all ReferencesDikstein et al. 1996a). Consistent with this hypothesis, these TAFs have no evident homologs in yeast and the activities ascribed to them are specific to multicellular organisms: (i) dTAFII110 and hTAFII130 are implicated in the response to Sp1, an activator that does not function in yeast, and (ii) hTAFII105 is thought to be involved in B-cell-specific gene expression (Dikstein et al. 1996axDikstein, R, Zhou, S, and Tjian, R. Cell. 1996; 87: 137–146Abstract | Full Text | Full Text PDF | PubMed | Scopus (151)See all ReferencesDikstein et al. 1996a). Thus, this family of TAFs may provide both for response to metazoan-specific activators and for cell-type-specific patterns of metazoan–gene transcription.The involvement of TAFs in complex patterns of gene transcription begs the question of why TAFs are used in yeast, an organism with a genome containing less than 6000 genes—little more than the approximately 4000 genes found in E. coli, where the analog of TFIID, σ, is a single polypeptide. In yeast, at least some introns—and hence the splicing machinery—are apparently used for coordinate regulation of ribosome biosynthesis by providing a feedback mechanism involving expression of ribosomal proteins (seeRymond and Rosbash 1992xSee all ReferencesRymond and Rosbash 1992). Perhaps, in yeast, the TAFs (and TBP) are an associated protein complex that has been conserved for coordinate regulation of gene expression: the finding that TAF depletion in yeast causes cell-cycle arrest suggests that TAFs permit coordinate regulation of genes involved in cell-cycle progression. Thus, just as σ factors are used to coordinately regulate genes in prokaryotes, the TAFs may also be used to coordinately regulate genes in eukaryotes.