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- Béve, Jenny
(author)
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Structure and function of the yeast mediator tail domain
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Mediator is a co-regulator complex that transduces regulatory information from activators and repressors to the RNA polymerase 11 transcription machinery. Mediator was originally discovered in Saccharomyces cerevisiae and since then Mediator-like complexes have been isolated in a number of organisms including mammals. S. cerevisiae Mediator can be divided into a head, a middle and a tail domain. The evolutionary conserved head and middle domains interact directly with RNA polymerase 11, whereas gene specific regulatory factors predominantly interact with the Mediator tail domain. The tail module is not well conserved between species and may have evolved to respond to species-specific gene regulatory requirements. The aim of this work is to increase the understanding of S. cerevisiae Mediator structure and function with a special emphasis on the tail domain. The main achievements presented here include the identification of Med9(Cse2), Med10(Nut2), Med11 and Med5(Nut1) as bona fide members of the S. cerevisiae Mediator (Paper I). The first purification and characterization of fission yeast Mediator (Paper II), which lacks a defined tail module and is much smaller than the related complexes from other cell types. The discovery of historic acetyltransferase activity localized to the S. cerevisiae Mediator subunit Med5 (Paper III), suggesting that Mediator under some circumstances can influence the chromatin structure of regulated genes. The finding that the cyklin dependent kinase Cdk8(srb10) phosphorylates the S. cerevisiae Mediator subunit in vitro and in vivo, and that this phosphorylation event specifically influence Mediator activity. (Paper IV). Finally, we perform and an in depth analysis of the Mediator component Med5 and demonstrate that this protein is a component of the tail domain and is required for the regulated expression of certain genes.
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| 4. |
- Zhu, Xuefeng, et al.
(author)
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Mediator influences telomeric silencing and cellular life span.
- 2011
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In: Molecular and cellular biology. - 1098-5549. ; 31:12, s. 2413-21
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Journal article (peer-reviewed)abstract
- The Mediator complex is required for the regulated transcription of nearly all RNA polymerase II-dependent genes. Here we demonstrate a new role for Mediator which appears to be separate from its function as a transcriptional coactivator. Mediator associates directly with heterochromatin at telomeres and influences the exact boundary between active and inactive chromatin. Loss of the Mediator Med5 subunit or mutations in Med7 cause a depletion of the complex from regions located near subtelomeric X elements, which leads to a change in the balance between the Sir2 and Sas2 proteins. These changes in turn result in increased levels of H4K16 acetylation near telomeres and in desilencing of subtelomeric genes. Increases in H4K16 acetylation have been observed at telomeres in aging cells. In agreement with this observation, we found that the loss of MED5 leads to shortening of the Saccharomyces cerevisiae (budding yeast) replicative life span.
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