title: Genome-wide location of the coactivator mediator: Binding without activation and transient Cdk8 interaction on DNA.
abstract: Mediator is a general coactivator of RNA polymerase II (Pol II) transcription. Genomic location analyses of different Mediator subunits indicate a uniformly composed core complex upstream of active genes but unexpectedly also upstream of inactive genes and on the coding regions of some highly active genes. The repressive Cdk8 submodule is associated with core Mediator at all sites but with a lower degree of occupancy, indicating transient interaction, regardless of promoter activity. This suggests gene-specific regulation of Cdk8 activity, rather than regulated Cdk8 recruitment. Mediator presence is not necessarily linked to transcription. This goes beyond Cdk8-repressed genes, indicating that Mediator can mark some regulatory regions ahead of additional signals. Overlap with intergenic Pol II location in stationary phase points to a role as a binding platform for inactive Pol II during quiescence. These results shed light on Cdk8 repression, suggest additional roles for Mediator, and query models of recruitment-coupled regulation.
authors.affiliation: Department of Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Andrau
authors.forename: Loes
authors.initials: L
authors.lastname: van de Pasch
authors.forename: Philip
authors.initials: P
authors.lastname: Lijnzaad
authors.forename: Theo
authors.initials: T
authors.lastname: Bijma
authors.forename: Marian Groot
authors.initials: MG
authors.lastname: Koerkamp
authors.forename: Jeroen
authors.initials: J
authors.lastname: van de Peppel
authors.forename: Michel
authors.initials: M
authors.lastname: Werner
authors.forename: Frank C P
authors.initials: FC
authors.lastname: Holstege
mesh_terms: D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000378:metabolism*; D021901:DNA, Intergenic; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016681:Genome, Fungal; D008954:Models, Biological; D021141:Nucleic Acid Amplification Techniques; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D021901:DNA, Intergenic; D005656:Fungal Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; C498309:SSN3 protein, S cerevisiae