A Triad of Subunits from the Gal11/Tail Domain of Srb Mediator Is an In Vivo Target of Transcriptional Activator Gcn4p

Zhang, Fan; Sumibcay, Laarni; Hinnebusch, Alan G.; Swanson, Mark J.

doi:10.1128/mcb.24.15.6871-6886.2004

Cited by 127 publications

(189 citation statements)

References 42 publications

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“…Here we find similar independent recruitment of the tail module to 3 RP genes and to CDC19 in srb4 ts yeast, despite loss of head and middle module recruitment. Similarly, Hinnebusch and coworkers observed continued Gcn4-mediated recruitment of the tail module in sin4⌬ yeast, while the head and middle modules were no longer recruited to the genes monitored (47). We observed loss of tail module association at RP genes in rap1 ts yeast, consistent with previous studies suggesting that the tail module is the principal target of activators (17,32).…”

Section: Discussionsupporting

confidence: 80%

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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Section: Discussionsupporting

confidence: 80%

Mediator complex association with constitutively transcribed genes in yeast

Ansari

Morse

2009

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

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“…1C, black bars) were both occupied by Med3. This observation is consistent with the requirement for Med3 in the establishment of a stable preinitiation complex (14,15) and its role in the recruitment of core Mediator (7,11).…”

Section: Cdk8supporting

confidence: 77%

Suppression of Mediator is regulated by Cdk8-dependent Grr1 turnover of the Med3 coactivator

González

Hamidi

Sol

et al. 2014

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

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Mediator, an evolutionary conserved large multisubunit protein complex with a central role in regulating RNA polymerase II-transcribed genes, serves as a molecular switchboard at the interface between DNA binding transcription factors and the general transcription machinery. Mediator subunits include the Cdk8 module, which has both positive and negative effects on activator-dependent transcription through the activity of the cyclin-dependent kinase Cdk8, and the tail module, which is required for positive and negative regulation of transcription, correct preinitiation complex formation in basal and activated transcription, and Mediator recruitment. Currently, the molecular mechanisms governing Mediator function remain largely undefined. Here we demonstrate an autoregulatory mechanism used by Mediator to repress transcription through the activity of distinct components of different modules. We show that the function of the tail module component Med3, which is required for transcription activation, is suppressed by the kinase activity of the Cdk8 module. Med3 interacts with, and is phosphorylated by, Cdk8; site-specific phosphorylation triggers interaction with and degradation by the Grr1 ubiquitin ligase, thereby preventing transcription activation. This active repression mechanism involving Grr1-dependent ubiquitination of Med3 offers a rationale for the substoichiometric levels of the tail module that are found in purified Mediator and the corresponding increase in tail components seen in cdk8 mutants.

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“…The Med2/3 pair interacts with Med15 to form a triad in yeast (Zhang et al, 2004). Notably, the human and plant Med2 and -3 sequences are closer than their fungal counterpart, whereas, apart from Med15N and parts of its middle region, there was less apparent structural similarity between the three organisms for Med15 (Fig.…”

Section: Structural Conservation Of Mediator Submodules In Plantsmentioning

confidence: 99%

The Mediator Complex in Plants: Structure, Phylogeny, and Expression Profiling of Representative Genes in a Dicot (Arabidopsis) and a Monocot (Rice) during Reproduction and Abiotic Stress

et al. 2011

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The Mediator (Med) complex relays regulatory information from DNA-bound transcription factors to the RNA polymerase II in eukaryotes. This macromolecular unit is composed of three core subcomplexes in addition to a separable kinase module. In this study, conservation of Meds has been investigated in 16 plant species representing seven diverse groups across the plant kingdom. Using Hidden Markov Model-based conserved motif searches, we have identified all the known yeast/metazoan Med components in one or more plant groups, including the Med26 subunits, which have not been reported so far for any plant species. We also detected orthologs for the Arabidopsis (Arabidopsis thaliana) Med32, -33, -34, -35, -36, and -37 in all the plant groups, and in silico analysis identified the Med32 and Med33 subunits as apparent orthologs of yeast/metazoan Med2/ 29 and Med5/24, respectively. Consequently, the plant Med complex appears to be composed of one or more members of 34 subunits, as opposed to 25 and 30 members in yeast and metazoans, respectively. Despite low similarity in primary Med sequences between the plants and their fungal/metazoan partners, secondary structure modeling of these proteins revealed a remarkable similarity between them, supporting the conservation of Med organization across kingdoms. Phylogenetic analysis between plant, human, and yeast revealed single clade relatedness for 29 Med genes families in plants, plant Meds being closer to human than to yeast counterparts. Expression profiling of rice (Oryza sativa) and Arabidopsis Med genes reveals that Meds not only act as a basal regulator of gene expression but may also have specific roles in plant development and under abiotic stress conditions.

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A Triad of Subunits from the Gal11/Tail Domain of Srb Mediator Is an In Vivo Target of Transcriptional Activator Gcn4p

Cited by 127 publications

References 42 publications

Mediator complex association with constitutively transcribed genes in yeast

Mediator complex association with constitutively transcribed genes in yeast

Suppression of Mediator is regulated by Cdk8-dependent Grr1 turnover of the Med3 coactivator

The Mediator Complex in Plants: Structure, Phylogeny, and Expression Profiling of Representative Genes in a Dicot (Arabidopsis) and a Monocot (Rice) during Reproduction and Abiotic Stress

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