Seminars in Cell & Developmental Biology 22 (2011) 759–768 Contents lists available at ScienceDirect Seminars in Cell & Developmental Biology jo urnal homepage: www.elsevier.com/locate/semcdb Review Interactions between subunits of the Mediator complex with gene-specific transcription factors ∗ Tilman Borggrefe , Xiaojing Yue Max-Planck-Institute of Immunobiology and Epigenetics, Stübeweg 51, D-79108 Freiburg, Germany a r t i c l e i n f o a b s t r a c t Article history: The Mediator complex forms the bridge between gene-specific transcription factors and the RNA poly- Available online 4 August 2011 merase II (RNAP II) machinery. Mediator is a large polypetide complex consisting of about thirty polypeptides that are mostly conserved from yeast to human. Mediator coordinates RNAP II recruit- Keywords: ment, phosphorylation of the C-terminal domain of RNAP II, enhancer-loop formation and post-initiation Mediator complex events. The focus of the review is to summarize the current knowledge of transcription factor/Mediator Transcriptional regulation interactions in higher eukaryotes and illuminate the physiological and gene-selective roles of Mediator. RNA polymerase © 2011 Elsevier Ltd. All rights reserved. Coactivator Contents 1. Introduction . 760 1.1. Discovery of the Mediator complex ... 760 1.2. Isolation of the mammalian Mediator complex . 760 1.3. Structure of the Mediator complex ... 760 1.4. Mediator is conserved throughout evolution . 761 1.5. The Mediator complex in transcriptional regulation ... 761 2. Mediator interaction with transcription factors. 762 2.1. MED1 interaction with transcription factors ... 762 2.1.1. MED1 in the Mediator complex . 762 2.1.2. MED1 interaction with nuclear receptors ... 762 2.1.3. MED1 interaction with GATA family of transcription factors . 762 ␤ 2.1.4. MED1 interaction with C/EBP . 762 2.2. MED15 interaction with transcription factors . 763 2.2.1. MED15 in TGF␤ signaling. 763 2.2.2. MED15 in lipid homeostasis . 763 2.3. MED23 interaction with transcription factors . 763 2.3.1. MED23 in MAPK signaling pathway . 763 2.3.2. MED23 in adipogenesis . 763 2.4. MED25 interaction with transcription factors . 763 2.4.1. MED25 interaction with VP16 . 763 2.4.2. MED25 in lipid metabolism through the interaction with HNF4 . 763 2.4.3. MED25 in chondrogenesis . 763 3. Mechanistic insights into the Mediator–activator interactions . 763 3.1. Synergy of several different Mediator subunits in gene-specific regulation . 763 3.1.1. REST . 763 3.1.2. Glucocortecoid Receptor . 764 3.1.3. PPAR␥ . 764 ∗ Corresponding author at: Department of Cellular and Molecular Immunology, Max-Planck-Institute of Immunobiology and Epigenetics, Stübeweg 51, D-79108 Freiburg, Germany. Tel.: +49 761 5108715. E-mail address: [email protected] (T. Borggrefe). 1084-9521/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.semcdb.2011.07.022 760 T. Borggrefe, X. Yue / Seminars in Cell & Developmental Biology 22 (2011) 759–768 3.2. Activator-induced conformational changes. 764 3.3. Variable association of Cdk8 submodule with the core Mediator . 764 4. Cdk8 submodule: implication in transcription repression and activation . 765 4.1. Cdk8 submodule in transcriptional repression . 765 4.1.1. RNAP II binding . 765 4.1.2. Phosphorylation of CTD, TFIIH and activators. ..