The RNA polymerase II holoenzyme and its implications for gene regulation

Koleske, Anthony J.; Young, Richard A.

doi:10.1016/s0968-0004(00)88977-x

Cited by 285 publications

(192 citation statements)

References 38 publications

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“…Moreover, our model does not negate the possibility that nascent TAR also attracts additional free Tat to increase transcriptional processivity (28). Similar to competing step-by-step assembly of the GTFs on the promoter (51) and the single-step binding of the holoenzyme (30), these modes of recruitment of Tat to the LTR might be complementary and additive. Future work on template commitment, the ability of TAR decoys to deplete Tat at different stages of transcription initiation and elongation, and pulse-chase analyses of Tat on initiating and elongating complexes will reveal further mechanistic details of these interactions among Tat, TAR, and the transcriptional machinery.…”

Section: Discussionmentioning

confidence: 95%

“…Recently, a large complex of proteins called the pol II holoenzyme has been identified in yeast and mammalian cells (30,36,41). The holoenzyme consists of a subset of GTFs, human SRBs (suppressors of mutations in polymerase B) which bind to the CTD and confer responsiveness to activators, and proteins involved in chromatin remodeling (SWI/SNF) and nucleotide excision repair (7,33,36,41,44,47).…”

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confidence: 99%

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The Human Immunodeficiency Virus Transactivator Tat Interacts with the RNA Polymerase II Holoenzyme

Cujec

Cho

Maldonado

et al. 1997

Molecular and Cellular Biology

108

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The human immunodeficiency virus (HIV) encodes a transcriptional transactivator (Tat), which binds to an RNA hairpin called the transactivation response element (TAR) that is located downstream of the site of initiation of viral transcription. Tat stimulates the production of full-length viral transcripts by RNA polymerase II (pol II). In this study, we demonstrate that Tat coimmunoprecipitates with the pol II holoenzyme in cells and that it binds to the purified holoenzyme in vitro. Furthermore, Tat affinity chromatography purifies a holoenzyme from HeLa nuclear extracts which, upon addition of TBP and TFIIB, supports Tat transactivation in vitro, indicating that it contains all the cellular proteins required for the function of Tat. By demonstrating that Tat interacts with the holoenzyme in the absence of TAR, our data suggest a single-step assembly of Tat and the transcription complex on the long terminal repeat of HIV.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

The Human Immunodeficiency Virus Transactivator Tat Interacts with the RNA Polymerase II Holoenzyme

Cujec

Cho

Maldonado

et al. 1997

Molecular and Cellular Biology

108

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show abstract

“…More recently a large multisubunit complex known as RNA pol II holoenzyme, containing RNA pol II, TFIIB, TFIIH and mediator [53,54] has been identified that can assemble independently of a promoter [44,45]. The identification of RNA pol II holoenzyme that is capable of responding to enhancers [43] suggests a different model for transcription-apparatus assembly.…”

Section: Figure 1 Gtf Assembly At a Typical Eukaryotic Promotermentioning

confidence: 99%

“…In this model, transcription enhancers first initiate the interaction of TFIID with the TATA box [34,55]. The same or other enhancers then interact with RNA pol II holoenzyme to facilitate its association with the TFIID-TFIIA promoter complex [53]. If we assume that stepwise and holoenzyme assembly occur simultaneously in i o, it is likely that the frequency of initiation may be increased by enhancers through RNA pol II holoenzyme recruitment.…”

Section: Figure 1 Gtf Assembly At a Typical Eukaryotic Promotermentioning

confidence: 99%

Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes

Ogbourne

Antalis

1998

Biochemical Journal

223

171

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Mechanisms controlling transcription and its regulation are fundamental to our understanding of molecular biology and, ultimately, cellular biology. Our knowledge of transcription initiation and integral factors such as RNA polymerase is considerable, and more recently our understanding of the involvement of enhancers and complexes such as holoenzyme and mediator has increased dramatically. However, an understanding of transcriptional repression is also essential for a complete understanding of promoter structure and the regulation of gene expression. Transcriptional repression in eukaryotes is achieved through ‘silencers ’, of which there are two types, namely ‘silencer elements ’ and ‘negative regulatory elements ’ (NREs). Silencer elements are classical, position-independent elements that direct an active repression mechanism, and NREs are position-dependent elements that direct a passive repression mechanism. In addition, ‘repressors ’ are DNA-binding trasncription factors that interact directly with silencers. A review of the recent literature reveals that it is the silencer itself and its context within a given promoter, rather than the interacting repressor, that determines the mechanism of repression. Silencers form an intrinsic part of many eukaryotic promoters and, consequently, knowledge of their interactive role with enchancers and other transcriptional elements is essential for our understanding of gene regulation in eukaryotes.

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“…Activation of class II gene transcription in eukaryotes involves the recruitment of a transcription initiation complex that includes the RNA polymerase II holoenzyme (1)(2)(3)(4)(5)(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)(8)(9)(10)(11).…”

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confidence: 99%

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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The RNA polymerase II holoenzyme and its implications for gene regulation

Cited by 285 publications

References 38 publications

The Human Immunodeficiency Virus Transactivator Tat Interacts with the RNA Polymerase II Holoenzyme

The Human Immunodeficiency Virus Transactivator Tat Interacts with the RNA Polymerase II Holoenzyme

Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes

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

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