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 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.
Mengeling
Brenda J
BJ
Section of Microbiology, One Shields Avenue, University of California, Davis 95616, CA, USA.
Lee
Sangho
S
Privalsky
Martin L
ML
D000818:Animals; D002460:Cell Line; D002645:Chickens; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism*; D019281:Dimerization; D051548:Histone Acetyltransferases / Q000378:metabolism; D056913:Mediator Complex Subunit 1; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D009930:Organic Chemicals / Q000494:pharmacology; D020218:Response Elements; D047490:Retinoid X Receptor alpha / Q000819:agonists / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism
C423914:LG 268; D056913:Mediator Complex Subunit 1; D051958:Nuclear Receptor Coactivator 2; D009930:Organic Chemicals; D047490:Retinoid X Receptor alpha; D037042:Thyroid Hormone Receptors beta; D015534:Trans-Activators; D014157:Transcription Factors; D014284:Triiodothyronine; D004247:DNA; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3