title: The Mediator complex in thyroid hormone receptor action.
abstract: BACKGROUND
  Mediator is an evolutionarily conserved multisubunit complex that plays an essential regulatory role in eukaryotic transcription of protein-encoding genes. The human complex was first isolated as a transcriptional coactivator bound to the thyroid hormone receptor (TR) and has since been shown to play a key coregulatory role for a broad range of nuclear hormone receptors (NRs) as well as other signal-activated transcription factors.
  
  
  METHODS
  We provide a general overview of Mediator structure and function, summarize the mechanisms by which Mediator is targeted to NRs, and outline recent evidence revealing Mediator as a regulatory axis for other distinct coregulatory factors, chromatin modifying enzymes and cellular signal transduction pathways.
  
  
  CONCLUSIONS
  Besides serving as a functional interface with the RNA polymerase II basal transcription machinery, Mediator plays a more versatile role in regulating transcription including the ability to: a) facilitate gene-specific chromatin looping events; b) coordinate chromatin modification events with preinitiation complex assembly; and c) regulate critical steps that occur during transcriptional elongation. The variably associated MED1 subunit continues to emerge as a pivotal player in Mediator function, not only as the primary interaction site for NRs, but also as a crucial interaction hub for other coregulatory factors, and as an important regulatory target for signal-activated kinases.
  
  
  CONCLUSIONS
  Mediator plays an integral coregulatory role at NR target genes by functionally interacting with the basal transcription apparatus and by coordinating the action of chromatin modifying enzymes and transcription elongation factors. This article is part of a Special Issue entitled Thyroid hormone signalling.
authors.affiliation: Department of Physiology & Biophysics, Robert Wood Johnson Medical School, UMDNJ, 683 Hoes Lane, Piscataway, NJ 08854-5635, USA. fondeljd@umdnj.edu
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fondell
mesh_terms: D000818:Animals; D006801:Humans; D056892:Mediator Complex / Q000235:genetics* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D056892:Mediator Complex; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone