Cdk11-CyclinL Controls the Assembly of the RNA Polymerase II Mediator Complex

• Published in: Cell reports (Cambridge) Vol. 2; no. 5; pp. 1068 - 1076
• Main Authors: Drogat, Julie, Migeot, Valérie, Mommaerts, Elise, Mullier, Caroline, Dieu, Marc, van Bakel, Harm, Hermand, Damien
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.11.2012; Elsevier
• Subjects: Amino Acid Sequence; Chromatin; Chromatin - metabolism; Cyclin-Dependent Kinase 8 - metabolism; Cyclin-Dependent Kinases - metabolism; Cyclins; Cyclins - metabolism; DNA-directed RNA polymerase; Gene Expression Profiling; Mediator Complex - genetics; Mediator Complex - metabolism; Molecular Sequence Data; Mutation; Phosphorylation; RNA Polymerase II - metabolism; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe; Schizosaccharomyces pombe Proteins - metabolism; Sequence Alignment; Transcription; Transcription, Genetic
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2012.09.027

The large Mediator (L-Mediator) is a general coactivator of RNA polymerase II transcription and is formed by the reversible association of the small Mediator (S-Mediator) and the kinase-module-harboring Cdk8. It is not known how the kinase module association/dissociation is regulated. We describe the fission yeast Cdk11-L-type cyclin pombe (Lcp1) complex and show that its inactivation alters the global expression profile in a manner very similar to that of mutations of the kinase module. Cdk11 is broadly distributed onto chromatin and phosphorylates the Med27 and Med4 Mediator subunits on conserved residues. The association of the kinase module and the S-Mediator is strongly decreased by the inactivation of either Cdk11 or the mutation of its target residues on the Mediator. These results show that Cdk11-Lcp1 regulates the association of the kinase module and the S-Mediator to form the L-Mediator complex. [Display omitted] ► A complex related to metazoan Cdk11-CyclinL is conserved in fission yeast ► Loss of either Cdk8 or Cdk11 similarly affects global expression profile ► Cdk11 phosphorylates two Mediator subunits ► Association of the Cdk8 module with the S-Mediator requires phosphorylation by Cdk11 The Mediator complex is essential for the expression of nearly all RNA polymerase II-dependent genes. Its four-subunit “kinase module,” harboring the Cdk8 kinase, can associate with the core S-Mediator (small Mediator) to form the L-Mediator (large Mediator). Hermand and colleagues have identified the Cdk11-Lcp1 complex in fission yeast as a key regulator of the reversible association between the kinase module and the S-Mediator by phosphorylating the Med27 and Med4 subunits.