MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription

Mol Cell. 2005 Jul 1;19(1):89-100. doi: 10.1016/j.molcel.2005.05.015.

Abstract

Human TRAP/Mediator is a key coactivator for many transcription factors that act through direct interactions with distinct subunits, and MED1/TRAP220 is the main subunit target for various nuclear receptors. Remarkably, the current study shows that MED1/TRAP220 only exists in a TRAP/Mediator subpopulation (less then 20% of the total) that is greatly enriched in specific TRAP/Mediator subunits and is tightly associated with a near stoichiometeric level of RNA polymerase II. Importantly, this MED1/TRAP220-containing holoenzyme supports both basal- and activator-dependent transcription in an in vitro system lacking additional RNA polymerase II. Furthermore, chromatin immunoprecipitation experiments demonstrate an activator-selective recruitment of MED1/TRAP220-containing versus MED1/TRAP220-deficient TRAP/Mediator complexes to estrogen receptor (ER) and p53 target genes, respectively. Finally, RNAi studies show that MED1/TRAP220 is required for ER-mediated transcription and estrogen-dependent breast cancer cell growth. These observations have significant implications for our current understanding of the composition, heterogeneity, and functional specificity of TRAP/Mediator complexes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism*
  • Escherichia coli / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Luciferases / metabolism
  • Mediator Complex Subunit 1
  • RNA Interference
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • MED1 protein, human
  • Mediator Complex Subunit 1
  • Receptors, Estrogen
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Luciferases
  • RNA Polymerase II
  • Endodeoxyribonucleases
  • MBD4 protein, human