Direct interactions between corepressors and coactivators permit the integration of nuclear receptor-mediated repression and activation.
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.
Duke Scholars
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription, Genetic
- Transcription Factors
- Thyroid Hormone Receptors beta
- Saccharomyces cerevisiae Proteins
- Repressor Proteins
- Recombinant Proteins
- Receptors, Thyroid Hormone
- Promoter Regions, Genetic
- Nuclear Receptor Coactivator 2
- Nuclear Receptor Coactivator 1
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription, Genetic
- Transcription Factors
- Thyroid Hormone Receptors beta
- Saccharomyces cerevisiae Proteins
- Repressor Proteins
- Recombinant Proteins
- Receptors, Thyroid Hormone
- Promoter Regions, Genetic
- Nuclear Receptor Coactivator 2
- Nuclear Receptor Coactivator 1