Activation of class II gene transcription by regulatory factors is potentiated by a novel activity

Meisterernst, Michael; Roy, Ananda L.; Lieu, Hsiao Mei; Roeder, Robert G.

doi:10.1016/0092-8674(91)90443-3

Cited by 302 publications

(251 citation statements)

References 53 publications

Supporting

Mentioning

237

Contrasting

Order By: Relevance

“…Sp1 was found to be the sole exception to this observation and, considering that Sp1 interacts with TAFs [34,35,78], TAF proteins were nominated as a second intermediary factor. Upstream stimulatory activity (' USA ') [79] is currently under investigation as a third intermediary factor, and others are likely to exist.…”

Section: Mechanisms Of Enhancer Mediated Regulationmentioning

confidence: 99%

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

Ogbourne

Antalis

1998

Biochemical Journal

222

171

View full text Add to dashboard Cite

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.

show abstract

Section: Mechanisms Of Enhancer Mediated Regulationmentioning

confidence: 99%

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

Ogbourne

Antalis

1998

Biochemical Journal

222

171

View full text Add to dashboard Cite

show abstract

“…These soluble cofactors were identified on the basis of their capacity to enhance activation of transcription in vitro (9)(10)(11)(12). In our initial study we had isolated a fraction from HeLa nuclear extracts, termed USA, for upstream factor stimulatory activity, that was essential for activator-dependent transcription in the presence of a complete set of general factors (9). Subsequent studies resolved the USA fraction into a minimum of four different positive cofactors, termed PC1 to PC4 (9)(10)(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

“…In our initial study we had isolated a fraction from HeLa nuclear extracts, termed USA, for upstream factor stimulatory activity, that was essential for activator-dependent transcription in the presence of a complete set of general factors (9). Subsequent studies resolved the USA fraction into a minimum of four different positive cofactors, termed PC1 to PC4 (9)(10)(11)(12)(13)(14)(15). Several specific components of the USA fraction and related cofactors have been characterized in recent years.…”

mentioning

confidence: 99%

“…There is also another group of coactivators that appear not to be integral parts of the basal machinery. These soluble cofactors were identified on the basis of their capacity to enhance activation of transcription in vitro (9)(10)(11)(12). In our initial study we had isolated a fraction from HeLa nuclear extracts, termed USA, for upstream factor stimulatory activity, that was essential for activator-dependent transcription in the presence of a complete set of general factors (9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Poly(ADP-ribose) polymerase enhances activator-dependent transcription in vitro

Meisterernst

Stelzer

Roeder

1997

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

Self Cite

151

126

View full text Add to dashboard Cite

Stimulation of class II gene transcription by activators requires the general factors and coactivators (1-4). Some of the coactivators are associated with TBP, the TATA box-binding protein, and RNA polymerase II, respectively (5-8). There is also another group of coactivators that appear not to be integral parts of the basal machinery. These soluble cofactors were identified on the basis of their capacity to enhance activation of transcription in vitro (9-12). In our initial study we had isolated a fraction from HeLa nuclear extracts, termed USA, for upstream factor stimulatory activity, that was essential for activator-dependent transcription in the presence of a complete set of general factors (9). Subsequent studies resolved the USA fraction into a minimum of four different positive cofactors, termed PC1 to PC4 (9-15). Several specific components of the USA fraction and related cofactors have been characterized in recent years. Examples include topoisomerase I, also called PC3 or Dr2 (13, 16), topoisomerase II (17), high mobility group proteins (18), and a protein called p15 or PC4 (14,15). Although PC1 and PC2 were discovered earlier, their identities are yet unresolved. Here we have identified human poly(ADP-ribose) polymerase (PARP) as one active component of the PC1 fraction.Mammalian PARP is a nuclear chromatin-associated protein of size 114 kDa that catalyzes the transfer of ADP-ribose units from NAD ϩ to nuclear protein acceptors (19)(20)(21)(22). Up to several hundred ADP-ribose units are transferred to PARP itself. Subsequently PARP modifies cellular proteins that are located within the chromatin. Target proteins include topoisomerases I and II, histones, and high mobility group proteins (23). The activity of PARP is strongly stimulated by the presence of nicks and strand breaks in DNA. These observations have contributed to the idea that PARP mediates stressinduced signaling and functions in an NAD-dependent manner in certain DNA repair processes (19,24,25). There is convincing evidence for the binding of PARP to damaged DNA containing single-strand breaks and nucleotide excisions. Automodification releases PARP from DNA, thus providing a mechanism for rendering DNA more accessible to the DNA repair machinery (23). In the absence of NAD, PARP inhibits DNA repair through binding to damaged DNA (26). Other functions proposed for PARP include roles in cellular NAD depletion (27), antirecombination and genomic stability (28), and DNA replication (29). PARP also serves as a marker for the onset of apoptosis, after which it is cleaved by proteases into DNA-binding and catalytic fragments (30).Earlier studies demonstrated that PARP suppresses nickinduced transcription in crude cell-free systems, whereas it was not required for basal transcription in systems reconstituted with purified factors (31). Moreover, inhibitors of PARP failed to demonstrate an essential role in transcription (32). However, PARP also proved to be nonessential in vivo for most of the functions suggested by the in vitro studie...

show abstract

“…The negative regulators that have been described include proteins purified for their ability to inhibit transcription in vitro (15)(16)(17)(18)(19)(20)(21) and genes identified because their products repress transcription from a subset of class II genes in vivo (21)(22)(23)(24)(25)(26)(27)(28)(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)(22)(23)(24), NOT1-4 (25)(26)(27), and SIN4 (28)(29) negatively regulate at least a subset of yeast genes in vivo.…”

mentioning

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.

View full text Add to dashboard Cite

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...

show abstract

Activation of class II gene transcription by regulatory factors is potentiated by a novel activity

Cited by 302 publications

References 53 publications

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

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

Poly(ADP-ribose) polymerase enhances activator-dependent transcription in vitro

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

Contact Info

Product

Resources

About