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Transcription: Why are TAFs essential?
R44
Dispatch
Transcription: Why are TAFs essential? Michael Hampsey and Danny Reinberg*
The TAFs are transcription factors associated with the TATA-binding protein, and until recently they were assumed to link specific activators to the general transcription machinery. Recent results suggest that the essential functions of TAFs are not as coactivators of transcription but as determinants of promoter selectivity. Address: *Howard Hughes Medical Institute and Department of Biochemistry, Division of Nucleic Acids Enzymology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA. Electronic identifier: 0960-9822-007-R0044 Current Biology 1997, 7:R44–R46 © Current Biology Ltd ISSN 0960-9822
The regulated transcription of genes by RNA polymerase II requires two distinct sets of factors. Members of one set are gene-specific and bind to promoters containing specific target sequences (reviewed in [1,2]). These factors either enhance or repress the rate of transcription in response to environmental signals. In contrast, the second set of factors are general transcription factors, required for the accurate initiation of most, and perhaps all, genes transcribed by RNA polymerase II. This second set includes TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH; these factors are sufficient to produce basal-level transcription in vitro in the absence of promoter-specific stimulation (reviewed in [3,4]). Assembly of the transcription preinitiation complex made up of these general factors is nucleated by TFIID; TFIID itself is composed of TBP, which binds the consensus sequence TATA, and TBPassociated factors or TAFs (reviewed in [5]). The mechanisms by which gene-specific factors interact with the general factors to modulate RNA synthesis are the subject of intense investigation and are critical for understanding cell growth and proliferation. A breakthrough in understanding the communication between activator molecules and the basal transcription machinery followed the finding by Tjian and colleagues (reviewed in [6]) that TBP, although sufficient for basallevel transcription, failed to support activated transcription in experimental systems derived from metazoan cells. Rather, activated transcription required the TFIID holocomplex. This led to the hypothesis that TAFs function as requisite ‘coactivators’, mediating the interaction between activators and the general transcription machinery (reviewed in [6]). This hypothesis predicts that TAFs interact directly both with the activation domains of specific activators and with general transcription factors.
Indeed, specific TAFs have been shown to interact with both activators and general transcription factors (reviewed in [5,6]), and there are no reported cases of transcriptional activation in higher eukaryotic systems in vitro in the absence of TFIID (with the exception of the TAT activator encoded by the human immunodeficiency virus). The same general factors are required for transcription in cell-free systems derived from both metazoan and yeast cells. Furthermore, comparisons among these factors have revealed extraordinary structural conservation. Only TFIID appeared to be an anomaly: whereas TBP isolated from mammalian and Drosophila cells was part of a tight complex with TAFs, yeast TBP was purified in monomeric form (reviewed in [5]). Subsequent immunoprecipitation experiments revealed that yeast TBP does exist in complexes with other polypeptides [7]. The cloning and characterization of these other proteins showed that some were TAFs specific to TFIID, and that others were components of different TBP–TAF complexes [8,9]. These results opened the door to determining the role of TAFs in vivo. Earlier results had suggested that TAFs might not be critical for activated transcription in yeast cell-free systems. A reconstituted yeast cell-free transcription system was developed that required the yeast counterparts of metazoan general factors for transcription (reviewed in [10]). As was the case for the metazoan cell-free systems, TBP was both necessary and sufficient for basal-level transcription. However, activated transcription in metazoan systems displays a strict requirement for TAFs as well as for other coactivator activities, whereas activated transcription in yeast requires a ‘mediator’ complex that is distinct from TFIID (reviewed in [10]). The mediator is a component of a large RNA polymerase II complex and is apparently devoid of TAFs [11]. Transcriptional activation in the absence of TAFs provides one apparent distinction between the yeast and higher eukaryotic in vitro systems. What, then, is the role of yeast TAFs in vivo? One approach to this question is to characterize the effect of TAF mutations in yeast. As was the case for the yeast genes encoding the general transcription factors, all TAF-encoding genes, with the exception of TFG3, which encodes TAFII30, are essential for cell viability. Remarkably, however, two recent studies from the Green [12] and Struhl [13] laboratories provide compelling evidence that transcriptional activation can occur in yeast in the absence of TAFs. Three different strategies were used to deplete cells of TAFs. In one study, TAFs were depleted either by shifting temperature-sensitive TAF
Dispatch
mutants (with defects in TAFII145 and TAFII150) to the non-permissive temperature, or by expressing TAF genes under the control of the glucose-repressible GAL promoter under repressing conditions [12]. In the other study, TAFs were depleted both by repression of TAF gene expression and by induced degradation of pre-existing TAF proteins [13]. The depletion of TAFs to less than 5 % of their normal level — estimated to result in less than 300 TAF molecules per cell — resulted in the rapid cessation of cell growth, as expected for the depletion of the products of essential genes. Strikingly, however, TAF depletion did not eliminate transcriptional activation of actively transcribed genes or of genes that were induced subsequent to TAF depletion. As expected, the depletion of TBP, TFIIB or the largest subunit of RNA polymerase II rapidly diminished activation. The two studies examined several TAFs, eliminating the concern that the failure to abolish transcriptional activation might be specific to a particular TAF. Moreover, depletion of TAFII145, the homologue of metazoan TAFII250 which is required for the formation of the TFIID complex, diminished the levels of the other TAF proteins without affecting activation. These results led to the conclusion that TAFs are not generally required for transcriptional activation in yeast. How is this conclusion to be reconciled with the premise that TAFs are requisite coactivators of transcription in higher eukaryotes? One concern is potential functional redundancy among the TAFs — the coactivator function of one TAF might be compensated for by another. This seems unlikely as the depletion of TAFII145 appeared to diminish the entire TFIID complex. Another potential concern is that the studies of living yeast cells simply looked at the wrong genes. However, the activated expression of several different classes of genes were looked at in the two studies, including genes that lacked the canonical TATA motif in their promoter regions. Interestingly, this latter group of genes appears to be the exception, in that their activation was found to be dependent upon TAFII19 and TAFII130. Rather than a role in coactivation, might the essential function of TAFs be the recognition of promoters that lack a canonical TATA motif? This possibility is supported by the finding that TFIID, but not TBP, is able to discriminate among distinct core promoters [14,15], and by the finding that Drosophila TAFII150 binds specifically to sequences around the transcription start site [16]. Accordingly, the requirement for TAFII19 and TAFII130 for the activation of yeast promoters that lack the TATA motif might reflect a role for these TAFs in promoter selectivity and the nucleation of a functional preinitiation complex. It is therefore possible that TFIID evolved not as a factor containing coactivator functions, but as a factor involved in promoter recognition, be it the TATA element through TBP, or other promoter elements through the TAFs.
R45
Figure 1 HeLa
S. cerevisiae
RNA polymerase II complex
RNA polymerase II complex
Purification
Purification
Core RNAPII
Core RNAPII
Mediator
Mediator
Activation
Activation
TBP + mediator + GTFs TFIID + mediator + GTFs
TBP + mediator + GTFs
+
+
© 1997 Current Biology
The essential difference between the requirements for transcriptional activation in metazoan (HeLa) and yeast (Saccharomyces cerevisiae) cell-free systems. Nearly identical purification procedures are used to isolate core RNA polymerase II (RNAPII) and the ‘mediator’ complex from the two systems. Whereas TBP, along with the other general transcription factors (GTFs) and mediator are sufficient for transcriptional activation in the yeast system, activation using analogous components from the HeLa (or other metazoan-derived) systems is absolutely dependent upon TFIID.
Although it was generally assumed that TAFs are required for transcriptional activation in vivo, there is no direct support for this assumption. The first human TAF gene to be cloned was identified as CCG1, whose product, TAFII250, is required for passage through the G1 phase of the cell cycle [17]. It was subsequently demonstrated that a CCG1/TAFII250 mutant was defective in transcriptional activation of the cell-cycle-regulated cyclin A promoter, but there was no effect on transcription from the c-fos promoter [18]. A logical interpretation of these results is that overall transcription is unaffected in this mutant, but that the activation of a subset of genes required for cell-cycle progression is impaired. Although confirming the importance of TAFs in vivo, these results do not establish a general requirement for TAFs in the activation of transcription. In agreement with these observations, Green and coworkers [12,19] found that conditional defects in three different TAFs (TAFII90, TAFII145 and TAFII150) blocked progression through two different stages of the yeast cell cycle. Thus, in higher eukaryotes as well as in yeast, TAFs appear to play a critical role in progression through the cell cycle, probably by affecting the regulation of specific genes. Taken together, these results support the conclusion that TAFs are not generally required for regulated transcription in vivo. In this sense, there appears to be no discrepancy between the requirement for TAFs in yeast and metazoan
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Current Biology, Vol 7 No 1
cells. The main controversy seems to reside in the studies in vitro: yeast cell-free transcription systems are not dependent upon TAFs, whereas all metazoan cell-free systems described to date are critically dependent upon TAFs for transcriptional activation. The cast of characters, including TAFs, and the fundamental mechanism of transcription initiation, appear to be remarkably conserved between yeast and higher eukaryotes. Both systems require all of the components of the basal transcription machinery as well as a mediator complex other than TFIID. The distinction in TAF requirement is found despite the almost identical experimental approaches that have been used to assay transcriptional activation in vitro (Fig. 1) [11,20,21]. This might represent a fundamental distinction between the functions of TAFs in yeast and metazoan systems. (As a cautionary note, the absence of TAFs from the mediator complex has not been unequivocally demonstrated.) It is possible that the mechanism of gene regulation in higher eukaryotes has acquired additional complexity as a result of the larger number of genes that need to be regulated: yeast contain approximately 6 000 genes, compared with approximately 100 000 genes in human cells. More importantly, the activation of metazoan genes responds to developmental as well as physiological signals, whereas yeast genes respond primarily to physiological cues. We hypothesize that TAFs evolved to serve a critical function in transcription, perhaps mediating alternative pathways of promoter recognition that are independent of the TATA motif. In higher eukaryotes, however, TAFs have evolved to acquire a more strict coactivator function in response to the increased requirement for expression and regulation of more complex genomes. This acquired function then became imprinted in metazoan organisms such that TAFs also serve a critical function in activation of transcription. Acknowledgments We are grateful to George Orphanides, Sasha Akoulitchev and Ramin Shiekhattar for valuable comments on the text.
References 1. Tjian R, Maniatis T: Transcriptional activation: a complex puzzle with few easy pieces. Cell 1994, 77:5–8. 2. Zawel L, Reinberg D: Common themes in assembly and function of eukaryotic transcription complexes. Annu Rev Biochem 1995, 64:533–561. 3. Orphanides G, LaGrange T, Reinberg D: The general initiation factors of RNA polymerase II. Genes Dev 1996, 10:2657–2683. 4. Roeder RG: The role of general initiation factors in transcription by RNA polymerase II. Trends Biochem Sci 1996, 21:327–335. 5. Burley SK, Roeder RG: Biochemistry and structural biology of transcription factor IID (TFIID). Annu Rev Biochem 1996, 65:769–799. 6. Verrijzer CP, Tjian R: TAFs mediate transcriptional activation and promoter selectivity. Trends Biochem Sci 1996, 21:338–342. 7. Poon D, Weil PA: Immunopurification of yeast TATA-binding protein and associated factors. Presence of transcription factor IIIB transcriptional activity. J Biol Chem 1993, 268:15325–15328.
8. Reese JC, Apone L, Walker SS, Griffin LA, Green MR: Yeast TAF(II)s in a multisubunit complex required for activated transcription. Nature 1994, 371:523–527. 9. Poon D, Bai Y, Campbell AM, Bjorklund S, Kim YJ, Zhou S, Kornberg RD, Weil PA: Identification and characterization of a TFIID-like multiprotein complex from Saccharomyces cerevisiae. Proc Natl Acad Sci USA 1995, 92:8224–8228. 10. Bjorklund S, Kim Y-J: Mediator of transciptional regulation. Trends Biochem Sci 1996, 21:335–337. 11. Kim Y-J, Bjorklund S, Li Y, Sayre MH, Kornberg RD: A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell 1994, 77:599–608. 12. Walker SS, Reese JC, Apone LM, Green MR: Transcription activation in cells lacking TAF(II)s. Nature 1996, 383:185–188. 13. Moqtaderi Z, Bai Y, Poon D, Weil PA, Struhl K: TBP-associated factors are not generally required for transcriptional activation in yeast. Nature 1996, 383:188–191. 14. Verrijzer CP, Chen JL, Yokomori K, Tjian R: Binding of TAFs to core elements directs promoter selectivity by RNA polymerase II. Cell 1995, 81:1115–1125. 15. Burke TW, Kadonaga JT: Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-box-deficient promoters. Genes Dev 1996, 10:711–724. 16. Verrijzer CP, Yokomori K, Chen JL, Tjian R: Drosophila TAFII150: similarity to yeast gene TSM-1 and specific binding to core promoter DNA. Science 1994, 264:933–941. 17. Ruppert S, Wang EH, Tjian R: Cloning and expression of human TAFII250: a TBP-associated factor implicated in cell-cycle regulation. Nature 1993, 362:175–179. 18. Wang EH, Tjian R: Promoter-selective transcriptional defect in cell cycle mutant ts13 rescued by hTAFII250. Science 1994, 263:811–814. 19. Apone LM, Virbasius CMA, Reese JC, Green MR: Yeast TAF(II)90 is required for cell-cycle progression through G(2)/M but not for general transcription activation. Genes Dev 1996, 10:2368–2380. 20. Maldonado E, Shiekhattar R, Sheldon M, Cho H, Drapkin R, Rickert P, Lees E, Anderson CW, Linn S, Reinberg D: A human RNA polymerase II complex associated with SRB and DNA-repair proteins. Nature 1996, 381:86–89. 21. Koleske AJ, Young RA: An RNA polymerase II holoenzyme responsive to activators. Nature 1994, 368:466–469.
Dispatch
Transcription: Why are TAFs essential? Michael Hampsey and Danny Reinberg*
The TAFs are transcription factors associated with the TATA-binding protein, and until recently they were assumed to link specific activators to the general transcription machinery. Recent results suggest that the essential functions of TAFs are not as coactivators of transcription but as determinants of promoter selectivity. Address: *Howard Hughes Medical Institute and Department of Biochemistry, Division of Nucleic Acids Enzymology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA. Electronic identifier: 0960-9822-007-R0044 Current Biology 1997, 7:R44–R46 © Current Biology Ltd ISSN 0960-9822
The regulated transcription of genes by RNA polymerase II requires two distinct sets of factors. Members of one set are gene-specific and bind to promoters containing specific target sequences (reviewed in [1,2]). These factors either enhance or repress the rate of transcription in response to environmental signals. In contrast, the second set of factors are general transcription factors, required for the accurate initiation of most, and perhaps all, genes transcribed by RNA polymerase II. This second set includes TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH; these factors are sufficient to produce basal-level transcription in vitro in the absence of promoter-specific stimulation (reviewed in [3,4]). Assembly of the transcription preinitiation complex made up of these general factors is nucleated by TFIID; TFIID itself is composed of TBP, which binds the consensus sequence TATA, and TBPassociated factors or TAFs (reviewed in [5]). The mechanisms by which gene-specific factors interact with the general factors to modulate RNA synthesis are the subject of intense investigation and are critical for understanding cell growth and proliferation. A breakthrough in understanding the communication between activator molecules and the basal transcription machinery followed the finding by Tjian and colleagues (reviewed in [6]) that TBP, although sufficient for basallevel transcription, failed to support activated transcription in experimental systems derived from metazoan cells. Rather, activated transcription required the TFIID holocomplex. This led to the hypothesis that TAFs function as requisite ‘coactivators’, mediating the interaction between activators and the general transcription machinery (reviewed in [6]). This hypothesis predicts that TAFs interact directly both with the activation domains of specific activators and with general transcription factors.
Indeed, specific TAFs have been shown to interact with both activators and general transcription factors (reviewed in [5,6]), and there are no reported cases of transcriptional activation in higher eukaryotic systems in vitro in the absence of TFIID (with the exception of the TAT activator encoded by the human immunodeficiency virus). The same general factors are required for transcription in cell-free systems derived from both metazoan and yeast cells. Furthermore, comparisons among these factors have revealed extraordinary structural conservation. Only TFIID appeared to be an anomaly: whereas TBP isolated from mammalian and Drosophila cells was part of a tight complex with TAFs, yeast TBP was purified in monomeric form (reviewed in [5]). Subsequent immunoprecipitation experiments revealed that yeast TBP does exist in complexes with other polypeptides [7]. The cloning and characterization of these other proteins showed that some were TAFs specific to TFIID, and that others were components of different TBP–TAF complexes [8,9]. These results opened the door to determining the role of TAFs in vivo. Earlier results had suggested that TAFs might not be critical for activated transcription in yeast cell-free systems. A reconstituted yeast cell-free transcription system was developed that required the yeast counterparts of metazoan general factors for transcription (reviewed in [10]). As was the case for the metazoan cell-free systems, TBP was both necessary and sufficient for basal-level transcription. However, activated transcription in metazoan systems displays a strict requirement for TAFs as well as for other coactivator activities, whereas activated transcription in yeast requires a ‘mediator’ complex that is distinct from TFIID (reviewed in [10]). The mediator is a component of a large RNA polymerase II complex and is apparently devoid of TAFs [11]. Transcriptional activation in the absence of TAFs provides one apparent distinction between the yeast and higher eukaryotic in vitro systems. What, then, is the role of yeast TAFs in vivo? One approach to this question is to characterize the effect of TAF mutations in yeast. As was the case for the yeast genes encoding the general transcription factors, all TAF-encoding genes, with the exception of TFG3, which encodes TAFII30, are essential for cell viability. Remarkably, however, two recent studies from the Green [12] and Struhl [13] laboratories provide compelling evidence that transcriptional activation can occur in yeast in the absence of TAFs. Three different strategies were used to deplete cells of TAFs. In one study, TAFs were depleted either by shifting temperature-sensitive TAF
Dispatch
mutants (with defects in TAFII145 and TAFII150) to the non-permissive temperature, or by expressing TAF genes under the control of the glucose-repressible GAL promoter under repressing conditions [12]. In the other study, TAFs were depleted both by repression of TAF gene expression and by induced degradation of pre-existing TAF proteins [13]. The depletion of TAFs to less than 5 % of their normal level — estimated to result in less than 300 TAF molecules per cell — resulted in the rapid cessation of cell growth, as expected for the depletion of the products of essential genes. Strikingly, however, TAF depletion did not eliminate transcriptional activation of actively transcribed genes or of genes that were induced subsequent to TAF depletion. As expected, the depletion of TBP, TFIIB or the largest subunit of RNA polymerase II rapidly diminished activation. The two studies examined several TAFs, eliminating the concern that the failure to abolish transcriptional activation might be specific to a particular TAF. Moreover, depletion of TAFII145, the homologue of metazoan TAFII250 which is required for the formation of the TFIID complex, diminished the levels of the other TAF proteins without affecting activation. These results led to the conclusion that TAFs are not generally required for transcriptional activation in yeast. How is this conclusion to be reconciled with the premise that TAFs are requisite coactivators of transcription in higher eukaryotes? One concern is potential functional redundancy among the TAFs — the coactivator function of one TAF might be compensated for by another. This seems unlikely as the depletion of TAFII145 appeared to diminish the entire TFIID complex. Another potential concern is that the studies of living yeast cells simply looked at the wrong genes. However, the activated expression of several different classes of genes were looked at in the two studies, including genes that lacked the canonical TATA motif in their promoter regions. Interestingly, this latter group of genes appears to be the exception, in that their activation was found to be dependent upon TAFII19 and TAFII130. Rather than a role in coactivation, might the essential function of TAFs be the recognition of promoters that lack a canonical TATA motif? This possibility is supported by the finding that TFIID, but not TBP, is able to discriminate among distinct core promoters [14,15], and by the finding that Drosophila TAFII150 binds specifically to sequences around the transcription start site [16]. Accordingly, the requirement for TAFII19 and TAFII130 for the activation of yeast promoters that lack the TATA motif might reflect a role for these TAFs in promoter selectivity and the nucleation of a functional preinitiation complex. It is therefore possible that TFIID evolved not as a factor containing coactivator functions, but as a factor involved in promoter recognition, be it the TATA element through TBP, or other promoter elements through the TAFs.
R45
Figure 1 HeLa
S. cerevisiae
RNA polymerase II complex
RNA polymerase II complex
Purification
Purification
Core RNAPII
Core RNAPII
Mediator
Mediator
Activation
Activation
TBP + mediator + GTFs TFIID + mediator + GTFs
TBP + mediator + GTFs
+
+
© 1997 Current Biology
The essential difference between the requirements for transcriptional activation in metazoan (HeLa) and yeast (Saccharomyces cerevisiae) cell-free systems. Nearly identical purification procedures are used to isolate core RNA polymerase II (RNAPII) and the ‘mediator’ complex from the two systems. Whereas TBP, along with the other general transcription factors (GTFs) and mediator are sufficient for transcriptional activation in the yeast system, activation using analogous components from the HeLa (or other metazoan-derived) systems is absolutely dependent upon TFIID.
Although it was generally assumed that TAFs are required for transcriptional activation in vivo, there is no direct support for this assumption. The first human TAF gene to be cloned was identified as CCG1, whose product, TAFII250, is required for passage through the G1 phase of the cell cycle [17]. It was subsequently demonstrated that a CCG1/TAFII250 mutant was defective in transcriptional activation of the cell-cycle-regulated cyclin A promoter, but there was no effect on transcription from the c-fos promoter [18]. A logical interpretation of these results is that overall transcription is unaffected in this mutant, but that the activation of a subset of genes required for cell-cycle progression is impaired. Although confirming the importance of TAFs in vivo, these results do not establish a general requirement for TAFs in the activation of transcription. In agreement with these observations, Green and coworkers [12,19] found that conditional defects in three different TAFs (TAFII90, TAFII145 and TAFII150) blocked progression through two different stages of the yeast cell cycle. Thus, in higher eukaryotes as well as in yeast, TAFs appear to play a critical role in progression through the cell cycle, probably by affecting the regulation of specific genes. Taken together, these results support the conclusion that TAFs are not generally required for regulated transcription in vivo. In this sense, there appears to be no discrepancy between the requirement for TAFs in yeast and metazoan
R46
Current Biology, Vol 7 No 1
cells. The main controversy seems to reside in the studies in vitro: yeast cell-free transcription systems are not dependent upon TAFs, whereas all metazoan cell-free systems described to date are critically dependent upon TAFs for transcriptional activation. The cast of characters, including TAFs, and the fundamental mechanism of transcription initiation, appear to be remarkably conserved between yeast and higher eukaryotes. Both systems require all of the components of the basal transcription machinery as well as a mediator complex other than TFIID. The distinction in TAF requirement is found despite the almost identical experimental approaches that have been used to assay transcriptional activation in vitro (Fig. 1) [11,20,21]. This might represent a fundamental distinction between the functions of TAFs in yeast and metazoan systems. (As a cautionary note, the absence of TAFs from the mediator complex has not been unequivocally demonstrated.) It is possible that the mechanism of gene regulation in higher eukaryotes has acquired additional complexity as a result of the larger number of genes that need to be regulated: yeast contain approximately 6 000 genes, compared with approximately 100 000 genes in human cells. More importantly, the activation of metazoan genes responds to developmental as well as physiological signals, whereas yeast genes respond primarily to physiological cues. We hypothesize that TAFs evolved to serve a critical function in transcription, perhaps mediating alternative pathways of promoter recognition that are independent of the TATA motif. In higher eukaryotes, however, TAFs have evolved to acquire a more strict coactivator function in response to the increased requirement for expression and regulation of more complex genomes. This acquired function then became imprinted in metazoan organisms such that TAFs also serve a critical function in activation of transcription. Acknowledgments We are grateful to George Orphanides, Sasha Akoulitchev and Ramin Shiekhattar for valuable comments on the text.
References 1. Tjian R, Maniatis T: Transcriptional activation: a complex puzzle with few easy pieces. Cell 1994, 77:5–8. 2. Zawel L, Reinberg D: Common themes in assembly and function of eukaryotic transcription complexes. Annu Rev Biochem 1995, 64:533–561. 3. Orphanides G, LaGrange T, Reinberg D: The general initiation factors of RNA polymerase II. Genes Dev 1996, 10:2657–2683. 4. Roeder RG: The role of general initiation factors in transcription by RNA polymerase II. Trends Biochem Sci 1996, 21:327–335. 5. Burley SK, Roeder RG: Biochemistry and structural biology of transcription factor IID (TFIID). Annu Rev Biochem 1996, 65:769–799. 6. Verrijzer CP, Tjian R: TAFs mediate transcriptional activation and promoter selectivity. Trends Biochem Sci 1996, 21:338–342. 7. Poon D, Weil PA: Immunopurification of yeast TATA-binding protein and associated factors. Presence of transcription factor IIIB transcriptional activity. J Biol Chem 1993, 268:15325–15328.
8. Reese JC, Apone L, Walker SS, Griffin LA, Green MR: Yeast TAF(II)s in a multisubunit complex required for activated transcription. Nature 1994, 371:523–527. 9. Poon D, Bai Y, Campbell AM, Bjorklund S, Kim YJ, Zhou S, Kornberg RD, Weil PA: Identification and characterization of a TFIID-like multiprotein complex from Saccharomyces cerevisiae. Proc Natl Acad Sci USA 1995, 92:8224–8228. 10. Bjorklund S, Kim Y-J: Mediator of transciptional regulation. Trends Biochem Sci 1996, 21:335–337. 11. Kim Y-J, Bjorklund S, Li Y, Sayre MH, Kornberg RD: A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell 1994, 77:599–608. 12. Walker SS, Reese JC, Apone LM, Green MR: Transcription activation in cells lacking TAF(II)s. Nature 1996, 383:185–188. 13. Moqtaderi Z, Bai Y, Poon D, Weil PA, Struhl K: TBP-associated factors are not generally required for transcriptional activation in yeast. Nature 1996, 383:188–191. 14. Verrijzer CP, Chen JL, Yokomori K, Tjian R: Binding of TAFs to core elements directs promoter selectivity by RNA polymerase II. Cell 1995, 81:1115–1125. 15. Burke TW, Kadonaga JT: Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-box-deficient promoters. Genes Dev 1996, 10:711–724. 16. Verrijzer CP, Yokomori K, Chen JL, Tjian R: Drosophila TAFII150: similarity to yeast gene TSM-1 and specific binding to core promoter DNA. Science 1994, 264:933–941. 17. Ruppert S, Wang EH, Tjian R: Cloning and expression of human TAFII250: a TBP-associated factor implicated in cell-cycle regulation. Nature 1993, 362:175–179. 18. Wang EH, Tjian R: Promoter-selective transcriptional defect in cell cycle mutant ts13 rescued by hTAFII250. Science 1994, 263:811–814. 19. Apone LM, Virbasius CMA, Reese JC, Green MR: Yeast TAF(II)90 is required for cell-cycle progression through G(2)/M but not for general transcription activation. Genes Dev 1996, 10:2368–2380. 20. Maldonado E, Shiekhattar R, Sheldon M, Cho H, Drapkin R, Rickert P, Lees E, Anderson CW, Linn S, Reinberg D: A human RNA polymerase II complex associated with SRB and DNA-repair proteins. Nature 1996, 381:86–89. 21. Koleske AJ, Young RA: An RNA polymerase II holoenzyme responsive to activators. Nature 1994, 368:466–469.