%0 Journal Article %T Mediator regulates non-coding RNA transcription at fission yeast centromeres %A Michael Thorsen %A Heidi Hansen %A Michela Venturi %A Steen Holmberg %A Genevieve Thon %J Epigenetics & Chromatin %D 2012 %I BioMed Central %R 10.1186/1756-8935-5-19 %X We found that the Med8-Med18-Med20 submodule of the Mediator complex is required for the transcriptional regulation of native centromeric dh and dg repeats and for the silencing of reporter genes inserted in centromeric heterochromatin. Mutations in the Med8-Med18-Med20 submodule did not alter Mediator occupancy at centromeres; however, they led to an increased recruitment of RNA polymerase II to centromeres and reduced levels of centromeric H3K9 methylation accounting for the centromeric desilencing. Further, we observed that Med18 and Med20 were required for efficient processing of dh transcripts into siRNA. Consistent with defects in centromeric heterochromatin, cells lacking Med18 or Med20 displayed elevated rates of mitotic chromosome loss.Our data demonstrate a role for the Med8-Med18-Med20 Mediator submodule in the regulation of non-coding RNA transcription at Schizosaccharomyces pombe centromeres. In wild-type cells this submodule limits RNA polymerase II access to the heterochromatic DNA of the centromeres. Additionally, the submodule may act as an assembly platform for the RNAi machinery or regulate the activity of the RNAi pathway. Consequently, Med8-Med18-Med20 is required for silencing of centromeres and proper mitotic chromosome segregation.Mediator is a large (approximately 1 MDa) protein complex that conveys regulatory signals to RNA polymerase II (Pol II). The Saccharomyces cerevisiae Mediator was the first to be characterized but Mediators have since then been described in many other species. A comparative genomics approach of approximately 70 eukaryotic genomes shows that although its exact subunit composition varies, Mediator is conserved across the eukaryotic kingdom [1]. The Schizosaccharomyces pombe Mediator consists of at least 20 subunits, all of which appear to have orthologues in Drosophila melanogaster, Caenorhabditis elegans and Homo sapiens[2].Three distinct domains (head, middle and tail) have been identified by electron microscopy on %K S. pombe %K Chromatin %K RNA Pol II %K Mediator %K Centromere %K Chromosome segregation %U http://www.epigeneticsandchromatin.com/content/5/1/19