title: Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.
abstract: The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism.
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Kuang-Lei
authors.initials: KL
authors.lastname: Tsai
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Chieri
authors.initials: C
authors.lastname: Tomomori-Sato
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Sato
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Biochemistry & Molecular Biology, Kansas University Medical Center, Kansas City, KS 66160, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Conaway
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Biochemistry & Molecular Biology, Kansas University Medical Center, Kansas City, KS 66160, USA.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Conaway
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: asturias@scripps.edu.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Asturias
mesh_terms: D020285:Cryoelectron Microscopy; D006367:HeLa Cells; D006801:Humans; D056892:Mediator Complex / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D008958:Models, Molecular; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D056892:Mediator Complex; D029701:Saccharomyces cerevisiae Proteins