Family of proteins that interact with TFIID and regulate promoter activity

Meisterernst, Michael; Roeder, Robert G.

doi:10.1016/0092-8674(91)90530-c

Cited by 310 publications

(209 citation statements)

References 38 publications

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“…These results extend the known negative regulatory effects of NC2 on core RNA polymerase II in vitro (16,17,20,(42)(43)(44)(47)(48)(49)(50) and confirm that this regulator can inhibit transcription by RNA polymerase II in vivo.…”

Section: Discussionsupporting

confidence: 70%

“…1b). A search of the GenBank database (June 7, 1996) revealed that the predicted protein has 39% identity over 99 aa to the NC2␣ (DRAP1) subunit of human NC2 (Dr1⅐DRAP1), which binds to TBP and represses transcription in vitro (16,17,20,(42)(43)(44)(47)(48)(49)(50). The gene encoding the putative yeast NC2␣ protein was named NCB1.…”

Section: Resultsmentioning

confidence: 99%

“…Several lines of evidence argue that NC2 acts globally as a repressor of most, if not all, class II genes. NC2 can repress transcription in vitro from a wide variety of mammalian, viral, and yeast promoters (16,20,(42)(43)(44)50). The NC2 suppressor mutation that compensates for reduced class II gene transcription in vivo due to loss of SRB4 also compensates for the global defect due to loss of SRB6 (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…The negative regulators that have been described include proteins purified for their ability to inhibit transcription in vitro (15-21) and genes identified because their products repress transcription from a subset of class II genes in vivo (21-29). For example, the human proteins NC1 (15, 16), NC2 or Dr1⅐DRAP1 (16,17,20), and DNA topoisomerase I (18, 19) repress basal transcription in vitro. The products of the yeast genes MOT1 (21-24), NOT1-4 (25-27), and SIN4 (28-29) negatively regulate at least a subset of yeast genes in vivo.…”

mentioning

confidence: 99%

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Functional antagonism between RNA polymerase II holoenzyme and global negative regulator NC2 in vivo

Gadbois

Chao

Reese

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Activation of eukaryotic class II gene expression involves the formation of a transcription initiation complex that includes RNA polymerase II, general transcription factors, and SRB components of the holoenzyme. Negative regulators of transcription have been described, but it is not clear whether any are general repressors of class II genes in vivo. We reasoned that defects in truly global negative regulators should compensate for deficiencies in SRB4 because SRB4 plays a positive role in holoenzyme function. Genetic experiments reveal that this is indeed the case: a defect in the yeast homologue of the human negative regulator NC2 (Dr1⅐DRAP1) suppresses a mutation in SRB4. Global defects in mRNA synthesis caused by the defective yeast holoenzyme are alleviated by the NC2 suppressing mutation in vivo, indicating that yeast NC2 is a global negative regulator of class II transcription. These results imply that relief from repression at class II promoters is a general feature of gene activation in vivo.Activation of class II gene transcription in eukaryotes involves the recruitment of a transcription initiation complex that includes the RNA polymerase II holoenzyme (1-6). The yeast RNA polymerase II holoenzyme is a large multisubunit complex containing RNA polymerase II, a subset of the general transcription factors, and SRB regulatory proteins (7-11). Mammalian RNA polymerase II holoenzymes have also been purified, and an SRB7 homologue has been identified as a component of those complexes (12)(13)(14).For some class II genes, regulation appears to involve both positive and negative transcriptional regulators. The negative regulators that have been described include proteins purified for their ability to inhibit transcription in vitro (15-21) and genes identified because their products repress transcription from a subset of class II genes in vivo (21-29). For example, the human proteins NC1 (15, 16), NC2 or Dr1⅐DRAP1 (16,17,20), and DNA topoisomerase I (18, 19) repress basal transcription in vitro. The products of the yeast genes MOT1 (21-24), NOT1-4 (25-27), and SIN4 (28-29) negatively regulate at least a subset of yeast genes in vivo. Whether any of these negative regulators are generally employed for class II gene regulation in vivo is not yet clear.The RNA polymerase II C-terminal domain and the associated SRB complex have been implicated in the response to transcriptional activators (7-9, 30, 31). Two holoenzyme components, SRB4 and SRB6, have been shown to play essential and positive roles in transcription at the majority of class II genes in Saccharomyces cerevisiae (32). We reasoned that a defect in SRB4 might be alleviated by defects in general negative regulators and that knowledge of such regulators could contribute to our understanding of the mechanisms involved in gene regulation in vivo. Here we show that a deficiency in yeast NC2 can compensate for the global transcriptional defects caused by mutations in the SRB4 and SRB6 subunits of the RNA polymerase II holoenzyme and that NC2 is a globa...

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Section: Discussionsupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Functional antagonism between RNA polymerase II holoenzyme and global negative regulator NC2 in vivo

Gadbois

Chao

Reese

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…5 The reporter gene plasmid (pTATA/130_PA×6) was constructed by inserting six repeats of the and HeLa nuclear extracts. The HeLa nuclear extracts were prepared as previously described 6 and was pre-incubated with a compound before adding nucleotides. After incubation at 30 °C for 60 min, the transcription reaction was terminated by adding 25 µL of a stop solution containing 1% SDA, 0.3 M sodium acetate (pH 5.2), 20 mM EDTA, and 1 mg/mL tRNA.…”

Section: Synthesis Of Compounds 1 Andmentioning

confidence: 99%