Mediator-Dependent Recruitment of TFIIH Modules in Preinitiation Complex

Esnault, Cyril; Ghavi-Helm, Yad; Brun, Sylvain; Soutourina, Julie; Berkum, Nynke Van; Boschiero, Claire; Holstege, Frank C.P.; Werner, Michel

doi:10.1016/j.molcel.2008.06.021

Cited by 142 publications

(157 citation statements)

References 59 publications

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“…Our structural and biochemical data along with relevant previous observations 12,17,23,24 suggests an interaction of the Pol II CTD, the Mediator Head module and TFIIH: First, mutation of Thr47 to Ala in Med11 affects the interaction of TFIIH with the Head module in vivo, resulting in a reduction of Pol II CTD Ser5 phosphorylation 17 . Thr47 of Med11 is located near the center of the two symmetrical long helical bundles of the Neck, which thus could constitute the docking surface for TFIIH ( Figure 4b)( Supplementary Fig.…”

Section: Derivatives (Supplementary Text 3)supporting

confidence: 72%

“…First, the Med18 loop region formed by residues 78-97 interacts with the Med17 CTH of the Fixed jaw domain ( Figure 3a, 3b). Second, the electron density corresponding to the N-terminus of the Med11 subunit (residues [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] indicates an interaction with Med18 (residues 17-27 and 281-289) ( Figure 3c, 3d). The assignment of Med11 residues 1-20 was complicated by the substitution of Met17 to Ser17 (see Methods), and thus an unambiguous sequence marker is lacking.…”

Section: Derivatives (Supplementary Text 3)mentioning

confidence: 99%

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Architecture of the mediator head module

Imasaki¹,

Wang²,

Tsai³

et al. 2011

Acta Cryst Sect A

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Mediator is a key regulator of eukaryotic transcription 1 , connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II (Pol II) 1-4 . In the yeast S. cerevisiae, Mediator comprises 25 subunits with a total mass over 1 MDa 5,6 , and is organized into three modules, termed Head, Middle/Arm and Tail 7-9 . Our understanding of Mediator assembly and its role in regulating transcription has been impeded to date by limited structural information. Here, we report the crystal structure of the essential Mediator Head module (seven subunits, 223 kDa) at 4.3 Å resolution. Our structure reveals three distinct domains with the integrity of the complex centered on a bundle of ten helices from five different Head subunits. An intricate pattern of interactions within this helical bundle ensures stable assembly of the Head subunits, and provides the binding sites for general transcription factors (GTFs) and Pol II. Our structural and functional data suggest the Head module to juxtapose TFIIH and the carboxyl-terminal domain (CTD) of the

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Section: Derivatives (Supplementary Text 3)supporting

confidence: 72%

Section: Derivatives (Supplementary Text 3)mentioning

confidence: 99%

Architecture of the mediator head module

Imasaki¹,

Wang²,

Tsai³

et al. 2011

Acta Cryst Sect A

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“…In addition to its association with active genes, Mediator has been reported to be present at some inactive gene promoters (26) and at nontranscribed regions of the yeast genome (30). To analyze Mediator presence on inactive genes, we used ChIP to monitor Srb5 and Rgr1 association with the SPO13 and PLM2 …”

Section: Mediator Associates Specifically With Several Constitutivelymentioning

confidence: 99%

Mediator complex association with constitutively transcribed genes in yeast

Ansari

Morse

2009

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

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Mediator is a large, multisubunit complex that is essential for transcription of mRNA by RNA Pol II in eukaryotes and is believed to bridge transcriptional activators and the general transcription machinery. However, several recent studies suggest that the requirement for Mediator during transcriptional activation is not universal, but rather activator dependent, and may be indirect for some genes. Here we have investigated Mediator association with several constitutively transcribed genes in yeast by comparing a yeast strain that harbors a temperature-sensitive mutation in an essential Mediator subunit, Srb4, with its wild-type (WT) counterpart. We find modest association of Mediator with constitutively active genes and show that this association is strongly decreased in srb4 ts yeast, whereas association with a nontranscribed region or repressed gene promoters is lower and unaffected in the mutant yeast. The tail module of Mediator remains associated with ribosomal protein (RP) gene promoters in srb4 ts yeast, while subunits from the head and middle modules are lost. Tail module association at Rap1-dependent gene promoters is lost in rap1 ts yeast, indicating that Rap1 is required for Mediator recruitment at these gene promoters and that its recruitment occurs via the tail module. Pol II association is also rapidly and severely affected in srb4 ts yeast, indicating that Mediator is directly required for pol II association at constitutively transcribed genes. Our results are consistent with Mediator functioning as a general transcription factor in yeast. Rap1 ͉ transcription

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“…Recently, we identified a direct interaction between the Med17 Mediator subunit and the Rpb3 Pol II subunit required for global Pol II transcription in vivo (Soutourina et al 2011). Previously, we showed that a direct contact between the Med11 subunit of Mediator and the Rad3 subunit of TFIIH is essential for the recruitment of the GTF to the PIC independently of Pol II (Esnault et al 2008). In addition to the crucial role of Mediator as a link between activators and the basal transcription machinery, recent studies suggest broader Mediator transcriptional functions, notably in the post-recruitment steps of transcription (Wang et al 2005;Takahashi et al 2011) and in DNA looping between the enhancers and promoters through a functional connection with cohesin (Kagey et al 2010).…”

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confidence: 99%

Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment

et al. 2013

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Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair. We identified a functional contact between the Med17 Mediator subunit and Rad2/XPG, the 39 endonuclease involved in nucleotide excision DNA repair. Genome-wide location analyses revealed that Rad2 is associated with RNA polymerase II (Pol II)-and Pol III-transcribed genes and telomeric regions in the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene promoters is well correlated with that of Mediator. Furthermore, UV sensitivity of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and concomitant decrease of Mediator interaction with Rad2 protein. Our results suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment to transcribed genes.

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Mediator-Dependent Recruitment of TFIIH Modules in Preinitiation Complex

Cited by 142 publications

References 59 publications

Architecture of the mediator head module

Architecture of the mediator head module

Mediator complex association with constitutively transcribed genes in yeast

Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment

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