Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 280, Issue 1-2, Pages 47-62Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2007.09.011
Keywords
thyroid hormone receptor; coactivator; transcriptional activation; coregualtor recruitment
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Funding
- NIDDK NIH HHS [R01 DK053528, R01 DK053528-10] Funding Source: Medline
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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 TR beta 0, can bind as trimers to a subset of naturally occurring DNA elements. We report here that this trimeric mode of DNA recognition by TR beta 0 also results in an enhanced recruitment of coactivators in vitro and increased transcriptional activation in cells compared to TR beta 0 dimers. At least part of this enhanced coactivator recruitment reflects a selectively enhanced avidity of the TR beta 0 trimer for a specific LXXLL interaction motif within the p 160 coactivators. TR beta 0 trimers also recruit certain coactivators at lower concentrations of T3 hormone and exhibit distinct coactivator stoichiometries than do TR beta 0 dimers. We conclude that trimer formation confers isoform-specific DNA recognition and transcriptional regulatory properties that are not observed for TR dimers. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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