Factors regulating the transcriptional elongation activity of RNA polymerase II

Shilatifard, Ali

doi:10.1096/fasebj.12.14.1437

Cited by 104 publications

(67 citation statements)

References 84 publications

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“…The TOP2 circular clamp formed in the presence of DNA could be immobile, which, similar to TOP2 covalent complexes, can also function as a roadblock for the Pol. Alternatively, the TOP2␤ circular clamp may be a sliding clamp (30), which may impede the ability of Pol to negotiate with the nucleosome (35,36). In either case, degradation of the TOP2␤ circular clamp could be the solution for recovery of the arrested Pol complex (see Fig.…”

Section: Discussionmentioning

confidence: 99%

The topoisomerase IIβ circular clamp arrests transcription and signals a 26S proteasome pathway

Xiao

Mao

Desai

et al. 2003

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

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It has been proposed that the topoisomerase II (TOP2)␤-DNA covalent complex arrests transcription and triggers 26S proteasome-mediated degradation of TOP2␤. It is unclear whether the initial trigger for proteasomal degradation is due to DNA damage or transcriptional arrest. In the current study we show that the TOP2 catalytic inhibitor 4,4-(2,3-butanediyl)-bis(2,6-piperazinedione) (ICRF-193), which traps TOP2 into a circular clamp rather than the TOP2-DNA covalent complex, can also arrest transcription. Arrest of transcription, which is TOP2␤-dependent, is accompanied by proteasomal degradation of TOP2␤. Different from TOP2 poisons and other DNA-damaging agents, ICRF-193 did not induce proteasomal degradation of the large subunit of RNA polymerase II. These results suggest that proteasomal degradation of TOP2␤ induced by the TOP2-DNA covalent complex or the TOP2 circular clamp is due to transcriptional arrest but not DNA damage. By contrast, degradation of the large subunit of RNA polymerase II is due to a DNA-damage signal.

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Section: Discussionmentioning

confidence: 99%

The topoisomerase IIβ circular clamp arrests transcription and signals a 26S proteasome pathway

Xiao

Mao

Desai

et al. 2003

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

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“…The initiation of chain synthesis proceeds through a cycle of abortive initiation events during which RNA-PII synthesizes short 2-10-nucleotide transcripts before escaping the promoter and entering a productive elongation mode (23). The activity of elongating RNAPII is modulated through the action of a number of elongation factors (24,25).The acidic activator GAL4-VP16 is a chimeric polypeptide composed of the DNA-binding domain of the yeast GAL4 protein (amino acids 1-147) and the transcriptional acidic activation domain of the viral protein VP16 (amino acids 412-490) (26). When GAL4 DNA-binding sites are located upstream of the TATA box of a promoter, this activator has been shown to stimulate transcription in a synergistic manner both in vivo and in vitro (see Ref.…”

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confidence: 99%

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confidence: 99%

Interactions of a DNA-bound Transcriptional Activator with the TBP-TFIIA-TFIIB-Promoter Quaternary Complex

Dion

Coulombe

2003

Journal of Biological Chemistry

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Site-specific protein-DNA photo-cross-linking was used to show that, when bound to its cognate site at various distances upstream of the TATA element, the chimeric transcriptional activator GAL4-VP16 can physically interact with a TATA box-binding protein (TBP)-transcription factor IIA (TFIIA)-TFIIB complex assembled on the TATA element. This result implies DNA bending and looping of promoter DNA as a result of the physical interaction between GAL4-VP16 and an interface of the TBP-TFIIA-TFIIB complex. This protein-protein interaction on promoter DNA minimally requires the presence of one GAL4 binding site and the formation of a quaternary complex containing TBP, TFIIB, and TFIIA on the TATA element. Notably, the topology of the TBP-TFIIA-TFIIB-promoter complex is not altered significantly by the interaction with DNA-bound activators. We also show that the ability of GAL4-VP16 to activate transcription through a single GAL4 binding site varies according to its precise location and orientation relative to the TATA element and that it can approach the efficiency obtained with multiple binding sites. Taken together, our results indicate that the spatial positioning of the DNA-bound activation domain is important for efficient activation, possibly by maximizing its interactions with the transcriptional machinery including the TBP-TFIIA-TFIIB-promoter quaternary complex.Most models of transcriptional activation imply a physical interaction of DNA-bound transcriptional activators and the transcription machinery assembled on core promoters (1-3). This contact between the activation domain and components of the transcription machinery has been attributed diverse functions including: (i) the recruitment of key transcription factors (e.g. general transcription factors or co-activators) at the promoter, (ii) the stimulation of enzymatic activities involved in the transcription reaction (e.g. promoter melting, phosphorylation, initiation of RNA chain synthesis), and (iii) the relief of transcriptional blockades induced by various types of repressors including nucleosomes. In support of this view of transcriptional activation, a number of protein-protein interactions between various activation domains and members of the RNA polymerase II (RNAPII) 1 transcription machinery have been characterized in solution and found to be important in mediating transcriptional activation (1-3). However, little is known about the formation of these protein-protein interactions when the interacting partners are bound to promoter DNA.Ultimately, transcriptional activators regulate the activity of the basal RNAPII transcription machinery. The transcription reaction is a multi-step process in which a preinitiation complex containing TBP, TFIIB, TFIIE, TFIIF, TFIIH, and RNA-PII is first assembled onto promoter DNA (4, 5). TBP recognizes and binds the TATA element, inducing a bend of about 80°in the DNA helix (6, 7). TFIIB binds to and stabilizes the TBP-promoter complex (8). TFIIF, a factor composed of two subunits called RAP74 and RAP30, binds ti...

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“…108,109 ELL can increase the catalytic rate of transcription elongation by Pol II from both promoter-independent and promoter-dependent templates. 108,[110][111][112] It contains a novel type of Pol II interaction domain that can repress polymerase activity in promoter-specific transcription in vitro. 110,113 The ELL protein can regulate both the transcriptional initiation and elongation activities of Pol II.…”

Section: Mll/ellmentioning

confidence: 99%

“…108,[110][111][112] It contains a novel type of Pol II interaction domain that can repress polymerase activity in promoter-specific transcription in vitro. 110,113 The ELL protein can regulate both the transcriptional initiation and elongation activities of Pol II. 109 The repression of transcription by ELL has been demonstrated to be due to its physical interaction with Pol II and the disruption of the formation of pre-initiation complex.…”

Section: Mll/ellmentioning

confidence: 99%

Transcription factors and translocations in lymphoid and myeloid leukemia

Crans¹,

Sakamoto²

2001

Leukemia

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Chromosomal translocations involving transcription factors and aberrant expression of transcription factors are frequently associated with leukemogenesis. Transcription factors are essential in maintaining the regulation of cell growth, development, and differentiation in the hematopoietic system. Alterations in the mechanisms that normally control these functions can lead to hematological malignancies. Further characterization of the molecular biology of leukemia will enhance our ability to develop disease-specific treatment strategies, and to develop effective methods of diagnosis and prognosis. Leukemia (2001) 15, 313-331.

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Factors regulating the transcriptional elongation activity of RNA polymerase II

Cited by 104 publications

References 84 publications

The topoisomerase IIβ circular clamp arrests transcription and signals a 26S proteasome pathway

The topoisomerase IIβ circular clamp arrests transcription and signals a 26S proteasome pathway

Interactions of a DNA-bound Transcriptional Activator with the TBP-TFIIA-TFIIB-Promoter Quaternary Complex

Transcription factors and translocations in lymphoid and myeloid leukemia

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