title: Mediator Undergoes a Compositional Change during Transcriptional Activation.
abstract: Mediator is a transcriptional co-activator recruited to enhancers by DNA-binding activators, and it also interacts with RNA polymerase (Pol) II as part of the preinitiation complex (PIC). We demonstrate that a single Mediator complex associates with the enhancer and core promoter in vivo, indicating that it can physically bridge these transcriptional elements. However, the Mediator kinase module associates strongly with the enhancer, but not with the core promoter, and it dissociates from the enhancer upon depletion of the TFIIH kinase. Severing the kinase module from Mediator by removing the connecting subunit Med13 does not affect Mediator association at the core promoter but increases occupancy at enhancers. Thus, Mediator undergoes a compositional change in which the kinase module, recruited via Mediator to the enhancer, dissociates from Mediator to permit association with Pol II and the PIC. As such, Mediator acts as a dynamic bridge between the enhancer and core promoter.
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors: Natalia
authors: N
authors: Petrenko
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors: Yi
authors: Y
authors: Jin
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Faculty of Health Sciences, University of Macau, Macau SAR, China. Electronic address: koonhowong@umac.mo.
authors: Koon Ho
authors: KH
authors: Wong
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kevin@hms.harvard.edu.
authors: Kevin
authors: K
authors: Struhl
mesh_terms: D001665:Binding Sites; D004742:Enhancer Elements, Genetic; D015966:Gene Expression Regulation, Fungal; D056892:Mediator Complex / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000235:genetics / Q000378:metabolism; D061785:Transcription Initiation, Genetic; D015533:Transcriptional Activation
chemical_list: D056892:Mediator Complex; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D051758:Transcription Factor TFIIH; D012319:RNA Polymerase II
keywords: RNA polymerase II; RNA polymerase II C-terminal domain; TFIIH kinase; enhancer; gene regulation; mediator; promoter; transcription; transcriptional co-activator