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Mol Cell Endocrinol. 2008 Jan 2;280(1-2):47-62. Epub 2007 Oct 6.

Coactivator recruitment is enhanced by thyroid hormone receptor trimers.

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Section of Microbiology, One Shields Avenue, University of California, Davis 95616, CA, USA.


Thyroid hormone receptors (TRs) are hormone-regulated transcription factors. TRs are generally thought to bind to their DNA target sites as homodimers or as TR/retinoid X receptor (RXR) heterodimers. However, we have shown that certain TR isoforms, such as TRbeta0, can bind as trimers to a subset of naturally occurring DNA elements. We report here that this trimeric mode of DNA recognition by TRbeta0 also results in an enhanced recruitment of coactivators in vitro and increased transcriptional activation in cells compared to TRbeta0 dimers. At least part of this enhanced coactivator recruitment reflects a selectively enhanced avidity of the TRbeta0 trimer for a specific LXXLL interaction motif within the p160 coactivators. TRbeta0 trimers also recruit certain coactivators at lower concentrations of T3 hormone and exhibit distinct coactivator stoichiometries than do TRbeta0 dimers. We conclude that trimer formation confers isoform-specific DNA recognition and transcriptional regulatory properties that are not observed for TR dimers.

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