Direct interactions between corepressors and coactivators permit the integration of nuclear receptor-mediated repression and activation

Mol Endocrinol. 2002 Jul;16(7):1482-91. doi: 10.1210/mend.16.7.0860.

Abstract

The unliganded thyroid hormone receptor beta (TRbeta) represses the basal transcriptional activity of target genes, in part through interactions with the nuclear receptor corepressor (N-CoR). In this study we have identified a rather unexpected interaction between N-CoR and the nuclear receptor coactivator ACTR. We have demonstrated in vitro and in intact cells that N-CoR directly associates with ACTR and that the interaction surfaces on N-CoR and ACTR are distinct from those required for TR binding. The significance of this finding was demonstrated by showing that N-CoR facilitates an interaction between unliganded-TRbeta and ACTR. One possible consequence of the formation of the trimeric complex of N-CoR/ACTR/unliganded-TR is that N-CoR may raise the local concentration of ACTR at target gene promoters. In support of this hypothesis it was demonstrated that the presence of N-CoR can enhance TRbeta-mediated transcriptional activation. It is proposed, therefore, that TRbeta- mediated activation and repression are integrally linked in a manner that is not predicted by the current models of nuclear receptor action.

Publication types

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

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Binding Sites
  • Cells, Cultured
  • Histone Acetyltransferases
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 2
  • Promoter Regions, Genetic
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Thyroid Hormone Receptors beta
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • NCOR1 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Coactivator 2
  • Receptors, Thyroid Hormone
  • Recombinant Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Thyroid Hormone Receptors beta
  • Transcription Factors
  • Acetyltransferases
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1