Coactivator recruitment is enhanced by thyroid hormone receptor trimers

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.