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Stefan G E Roberts - One of the best experts on this subject based on the ideXlab platform.

  • Interaction of the TFIIB zinc ribbon with RNA polymerase II.
    Biochemical Society transactions, 2008
    Co-Authors: Laura M Elsby, Stefan G E Roberts
    Abstract:

    Transcription by RNA polymerase II requires the assembly of the General Transcription Factors at the promoter to form a pre-initiation complex. The General Transcription Factor TF (Transcription Factor) IIB plays a central role in the assembly of the pre-initiation complex, providing a bridge between promoter-bound TFIID and RNA polymerase II/TFIIF. We have characterized a series of TFIIB mutants in their ability to support Transcription and recruit RNA polymerase II to the promoter. Our analyses identify several residues within the TFIIB zinc ribbon that are required for RNA polymerase II assembly. Using the structural models of TFIIB, we describe the interface between the TFIIB zinc ribbon region and RNA polymerase II.

  • core promoter elements recognized by Transcription Factor iib
    Biochemical Society Transactions, 2006
    Co-Authors: W Deng, Stefan G E Roberts
    Abstract:

    The General Transcription Factor TFIIB (Transcription Factor IIB) plays a critical role in the assembly of the RNA polymerase II pre-initiation complex. TFIIB can make sequence-specific DNA contacts both upstream and downstream of the TATA box. This has led to the definition of two core promoter BREs (TFIIB-recognition elements), one upstream [BRE u (upstream BRE)] and one downstream of TATA box [BRE d (downstream BRE)]. TFIIB–BRE u and TFIIB–BRE d contacts are mediated by two independent DNA-recognition motifs within the core domain of TFIIB. Both the BRE u and the BRE d modulate the Transcriptional potency of a promoter. However, the net effect of the BREs on promoter activity is dependent on the specific blend of elements present within a core promoter.

  • assembly of Transcription Factor iib at a promoter in vivo requires contact with rna polymerase ii
    EMBO Reports, 2006
    Co-Authors: Laura M Elsby, Amanda Odonnell, Laura Green, Andrew D Sharrocks, Stefan G E Roberts
    Abstract:

    The General Transcription Factor TFIIB has a central role in the assembly of the preinitiation complex at the promoter, providing a platform for the entry of RNA polymerase II/TFIIF. We used an RNA interference (RNAi)-based system in which TFIIB expression is ablated in vivo and replaced with a TFIIB derivative that contains a silent mutation and is refractory to the RNAi. Using this approach, we found that Transcriptionally defective TFIIB amino-terminal mutants showed distinct effects on the basis of their ability to compete with wild-type TFIIB in vivo. Moreover, analysis of the TFIIB mutant derivatives by chromatin immunoprecipitation showed that promoter occupancy by TFIIB is dependent on the association with RNA polymerase II. Together, our results support a mode of preinitiation complex assembly in which TFIIB/RNA polymerase II recruitment to the promoter occurs in vivo.

Danny Reinberg - One of the best experts on this subject based on the ideXlab platform.

  • New core promoter element in RNA polymerase II-dependent Transcription: sequence-specific DNA binding by Transcription Factor IIB
    Genes & development, 1998
    Co-Authors: Thierry Lagrange, Danny Reinberg, Achillefs N. Kapanidis, Hong Tang, Richard H. Ebright
    Abstract:

    A sequence element located immediately upstream of the TATA element, and having the consensus sequence 5'-G/C-G/C-G/A-C-G-C-C-3', affects the ability of Transcription Factor IIB to enter Transcription complexes and support Transcription initiation. The sequence element is recognized directly by the Transcription Factor IIB. Recognition involves alpha-helices 4' and 5' of IIB, which comprise a helix-turn-helix DNA-binding motif. These observations establish that Transcription initiation involves a fourth core promoter element, the IIB recognition element (BRE), in addition to the TATA element, the initiator element, and the downstream promoter element, and involves a second sequence-specific General Transcription Factor, IIB, in addition to Transcription Factor IID.

  • dual role of tfiih in dna excision repair and in Transcription by rna polymerase ii
    Nature, 1994
    Co-Authors: Ronny Drapkin, Joyce T. Reardon, Aziz Sancar, Leigh Zawel, Athar Ansari, Juch Chin Huang, Kyujeong Ahn, Danny Reinberg
    Abstract:

    THE RNA polymerase II General Transcription Factor TFIIH is composed of several polypeptides. The observation that the largest subunit of TFIIH is the excision-repair protein XPB/ERCC3 (ref. 1), a helicase implicated in the human DNA-repair disorders xeroderma pigmentosum (XP) and Cockayne's syndrome2,3, suggests a functional link between Transcription and DNA repair4,5. To understand the connection between these two cellular processes, we have extensively purified and functionally analysed TFIIH. We find that TFIIH has a dual role, being required for basal Transcription of class II genes and for participation in DNA-excision repair. TFIIH is shown to complement three different cell extracts deficient in excision repair: XPB/ERCC3, XPC and XPD/ ERCC2. The complementation of XPB and XPD is a consequence of ERCC3 and ERCC2 being integral subunits of TFIIH, whereas complementation of XPC is due to an association of this polypeptide with TFIIH. We found that the General Transcription Factor IIE negatively modulates the helicase activity of TFIIH through a direct interaction between TFIIE and the ERCC3 subunit of TFIIH.

  • human General Transcription Factor iih phosphorylates the c terminal domain of rna polymerase ii
    Nature, 1992
    Co-Authors: Leigh Zawel, Jean Marc Egly, Laurent Fisher, Danny Reinberg
    Abstract:

    Phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II is believed to control the transition from Transcription initiation to elongation. The General Transcription Factor IIH (TFIIH) contains a kinase activity capable of phosphorylating this domain. Factors that promote the association of RNA polymerase II with the preinitiation complex stimulate this activity. The Transcription Factor HE, which is required for the stable association of TFIIH with the preinitiation complex, affects the processivity of TFIIH kinase.

Roger D. Kornberg - One of the best experts on this subject based on the ideXlab platform.

  • Structural basis of Transcription: an RNA polymerase II-TFIIB cocrystal at 4.5 Angstroms.
    Science (New York N.Y.), 2004
    Co-Authors: David A. Bushnell, Kenneth D. Westover, Ralph E. Davis, Roger D. Kornberg
    Abstract:

    The structure of the General Transcription Factor IIB (TFIIB) in a complex with RNA polymerase II reveals three features crucial for Transcription initiation: an N-terminal zinc ribbon domain of TFIIB that contacts the “dock” domain of the polymerase, near the path of RNA exit from a transcribing enzyme; a “finger” domain of TFIIB that is inserted into the polymerase active center; and a C-terminal domain, whose interaction with both the polymerase and with a TATA box–binding protein (TBP)–promoter DNA complex orients the DNA for unwinding and Transcription. TFIIB stabilizes an early initiation complex, containing an incomplete RNA-DNA hybrid region. It may interact with the template strand, which sets the location of the Transcription start site, and may interfere with RNA exit, which leads to abortive initiation or promoter escape. The trajectory of promoter DNA determined by the C-terminal domain of TFIIB traverses sites of interaction with TFIIE, TFIIF, and TFIIH, serving to define their roles in the Transcription initiation process.

  • revised subunit structure of yeast Transcription Factor iih tfiih and reconciliation with human tfiih
    Journal of Biological Chemistry, 2003
    Co-Authors: Yuichiro Takagi, Hirofumi Komori, Weihau Chang, Andy Hudmon, Hediye Erdjumentbromage, Paul Tempst, Roger D. Kornberg
    Abstract:

    Tfb4 is identified as a subunit of the core complex of yeast RNA polymerase II General Transcription Factor IIH (TFIIH) by affinity purification, by peptide sequence analysis, and by expression of the entire complex in insect cells. Tfb3, previously identified as a component of the core complex, is shown instead to form a complex with cdk and cyclin subunits of TFIIH. This reassignment of subunits resolves a longstanding discrepancy between yeast and human TFIIH complexes.

  • subunits of yeast rna polymerase ii Transcription Factor tfiih encoded by the ccl1 gene
    Journal of Biological Chemistry, 1996
    Co-Authors: Jesper Q Svejstrup, William J Feaver, Roger D. Kornberg
    Abstract:

    Both 45- and 47-kDa subunits of TFIIK, a subcomplex of RNA polymerase II General Transcription Factor TFIIH, are encoded by the yeast cyclin gene CCL1. In all likelihood, these two subunits individually form cyclin-dependent kinase/cyclin dimers with Kin28 protein, a key enzyme in phosphorylation of the C-terminal domain of RNA polymerase II concomitant with Transcription.

George P Chrousos - One of the best experts on this subject based on the ideXlab platform.

  • Transcription Factor tfiih components enhance the gr coactivator activity but not the cell cycle arresting activity of the human immunodeficiency virus type 1 protein vpr
    Biochemical and Biophysical Research Communications, 2002
    Co-Authors: Tomoshige Kino, Makoto Tsukamoto, George P Chrousos
    Abstract:

    Abstract The human immunodeficiency virus type-1 (HIV-1)-accessory protein Vpr interacts with and potentiates the activity of the glucocorticoid receptor (GR) and arrests the host cell cycle at the G2/M boundary. Here we report that three core components of the General Transcription Factor (TF) IIH, CDK7, Cyclin H, and MAT1, enhance Vpr’s GR coactivator activity but inhibit its cell cycle-arresting function. A CDK7 mutant defective in kinase activity for the C-terminal tail of RNA polymerase II, which cannot form a functional TFIIH complex, did not enhance Vpr coactivator activity. Overexpression of all three TFIIH components and p300 cooperatively enhanced Vpr coactivator activity, whereas TFIIH overexpression did not potentiate the Transcriptional activity of a Vpr mutant, which does not bind p300/CBP. These findings suggest that TFIIH participates in Vpr’s GR coactivating activity, at a step beyond its interaction with p300/CBP.

  • the hiv 1 virion associated protein vpr is a coactivator of the human glucocorticoid receptor
    Journal of Experimental Medicine, 1999
    Co-Authors: Tomoshige Kino, Alexander Gragerov, Jeffrey B Kopp, Roland Stauber, George N Pavlakis, George P Chrousos
    Abstract:

    The HIV-1 virion-associated accessory protein Vpr affects both viral replication and cellular Transcription, proliferation, and differentiation. We report that Vpr enhances the activity of glucocorticoids in lymphoid and muscle-derived cell lines by interacting directly with the glucocorticoid receptor and General Transcription Factors, acting as a coactivator. Vpr contains the signature motif LXXLL also present in cellular nuclear receptor coactivators, such as steroid receptor coactivator 1 and p300/CREB-binding protein, which mediates their interaction with the glucocorticoid and other nuclear hormone receptors. A mutant Vpr molecule with disruption of this coactivator signature motif lost its ability to influence Transcription of glucocorticoid-responsive genes and became a dominant-negative inhibitor of Vpr, possibly by retaining its General Transcription Factor–binding activities. The glucocorticoid coactivator activity of Vpr may contribute to increased tissue glucocorticoid sensitivity in the absence of hypercortisolism and to the pathogenesis of AIDS.

Jean Marc Egly - One of the best experts on this subject based on the ideXlab platform.

  • In TFIIH the Arch domain of XPD is mechanistically essential for Transcription and DNA repair.
    Nature Communications, 2020
    Co-Authors: Stefan Peissert, Arnaud Poterszman, Jean Marc Egly, Jochen Kuper, Florian Sauer, Daniel Grabarczyk, Cathy Braun, Gudrun Sander, Caroline Kisker
    Abstract:

    The XPD helicase is a central component of the General Transcription Factor TFIIH which plays major roles in Transcription and nucleotide excision repair (NER). Here we present the high-resolution crystal structure of the Arch domain of XPD with its interaction partner MAT1, a central component of the CDK activating kinase complex. The analysis of the interface led to the identification of amino acid residues that are crucial for the MAT1-XPD interaction. More importantly, mutagenesis of the Arch domain revealed that these residues are essential for the regulation of (i) NER activity by either impairing XPD helicase activity or the interaction of XPD with XPG; (ii) the phosphorylation of the RNA polymerase II and RNA synthesis. Our results reveal how MAT1 shields these functionally important residues thereby providing insights into how XPD is regulated by MAT1 and defining the Arch domain as a major mechanistic player within the XPD scaffold.

  • human General Transcription Factor iih phosphorylates the c terminal domain of rna polymerase ii
    Nature, 1992
    Co-Authors: Leigh Zawel, Jean Marc Egly, Laurent Fisher, Danny Reinberg
    Abstract:

    Phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II is believed to control the transition from Transcription initiation to elongation. The General Transcription Factor IIH (TFIIH) contains a kinase activity capable of phosphorylating this domain. Factors that promote the association of RNA polymerase II with the preinitiation complex stimulate this activity. The Transcription Factor HE, which is required for the stable association of TFIIH with the preinitiation complex, affects the processivity of TFIIH kinase.

  • class ii b General Transcription Factor tfiib that binds to the template committed preinitiation complex is different from General Transcription Factor btf3
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: Vincent Moncollin, Jean Marc Egly, Laurent Fischer, Bruno Cavallini, Pierre Chambon
    Abstract:

    A class II (B) General Transcription Factor of 34 kDa has been purified from HeLa cells to apparent homogeneity. This Factor appears to be Transcription Factor IIB (TFIIB), since it binds in vitro to template-committed preinitiation complexes formed between a template containing the TATA box/cap-site elements of the adenovirus type 2 major late promoter (Ad2MLP) and recombinant human or yeast TFIID (previously called BTF1) expressed in Escherichia coli. DNase I footprint studies show an extended pattern of protection of Ad2MLP TATA box/cap-site sequences when TFIIB is bound to template-committed complexes, even though TFIIB does not bind on its own to the template in the absence of TFIID. We also show that TFIIB is different from BTF3 by a number of criteria.