Structure and function of CRSP/Med2; a promoter-selective transcriptional coactivator complex

Mol Cell. 2004 Jun 4;14(5):675-83. doi: 10.1016/j.molcel.2004.05.014.


The multi-subunit, human CRSP coactivator-also known as Mediator (Med)-regulates transcription by mediating signals between enhancer-bound factors (activators) and the core transcriptional machinery. Interestingly, different activators are known to bind distinct subunits within the CRSP/Med complex. We have isolated a stable, endogenous CRSP/Med complex (CRSP/Med2) that specifically lacks both the Med220 and the Med70 subunits. The three-dimensional structure of CRSP/Med2 was determined to 31 A resolution using electron microscopy and single-particle reconstruction techniques. Despite lacking both Med220 and Med70, CRSP/Med2 displays potent, activator-dependent transcriptional coactivator function in response to VP16, Sp1, and Sp1/SREBP-1a in vitro using chromatin templates. However, CRSP/Med2 is unable to potentiate activated transcription from a vitamin D receptor-responsive promoter, which requires interaction with Med220 for coactivator recruitment, whereas VDR-directed activation by CRSP/Med occurs normally. Thus, it appears that CRSP/Med may be regulated by a combinatorial assembly mechanism that allows promoter-selective function upon exchange of specific coactivator targets.

Publication types

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

MeSH terms

  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genes, Regulator / genetics*
  • HeLa Cells
  • Herpes Simplex Virus Protein Vmw65 / genetics
  • Herpes Simplex Virus Protein Vmw65 / metabolism
  • Humans
  • Macromolecular Substances
  • Promoter Regions, Genetic / genetics*
  • Protein Structure, Tertiary / physiology
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism
  • Sterol Regulatory Element Binding Protein 1
  • Trans-Activators / chemistry*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors*
  • Transcriptional Activation / genetics*
  • Vitamin D Response Element / genetics


  • CCAAT-Enhancer-Binding Proteins
  • CRSP protein, human
  • DNA-Binding Proteins
  • Herpes Simplex Virus Protein Vmw65
  • Macromolecular Substances
  • Protein Subunits
  • SREBF1 protein, human
  • Sp1 Transcription Factor
  • Sterol Regulatory Element Binding Protein 1
  • Trans-Activators
  • Transcription Factors