Genome-Wide Location of the Coactivator Mediator: Binding without Activation and Transient Cdk8 Interaction on DNA

• DOI: 10.1016/j.molcel.2006.03.023
• Publication Date: 2006-04-22T01:43:45Z
• Authors: Jean-Christophe A...; Loes van de Pasch; Philip Lijnzaad; Theo Bijma; Marian Groot Koer...; Jeroen van de Peppel; Michel Werner; Frank C.P. Holstege
• Keywords: 0301 basic medicine; Chromatin Immunoprecipitation; Binding Sites; Saccharomyces cerevisiae Proteins; Cell Biology; Saccharomyces cerevisiae; Cyclin-Dependent Kinase 8; Models, Biological; Polymerase Chain Reaction; Cyclin-Dependent Kinases; Enzyme Activation; Fungal Proteins; 03 medical and health sciences; Trans-Activators; DNA, Intergenic; RNA, Messenger; Genome, Fungal; DNA, Fungal; Promoter Regions, Genetic; Molecular Biology; Nucleic Acid Amplification Techniques; Oligonucleotide Array Sequence Analysis; Protein Binding

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.