A potential transcriptional adaptor(s) may be required in thyroid hormone-stimulated gene transcription in vitro.
Thyroid hormone (T3) stimulates gene transcription by activation of thyroid hormone receptors (TRs), which bind to thyroid hormone response elements in T3-regulated genes. Retinoid-X receptors (RXRs), major members of the TR auxiliary proteins, have recently been shown to form TR-RXR heterodimers, to enhance the binding of the TRs to thyroid hormone response elements, and to augment TR-mediated transcriptional activation. In this report, we provide evidence that a putative adaptor(s), other than RXR, may be involved in T3-stimulated gene transcription. First, T3-stimulated, but not basal, transcription from the rat GH promoter was progressively and specifically inhibited by the addition of increasing amounts of either GST-TR beta or GST-RXR beta in a cell-free in vitro transcription. Second, this specific transcriptional inhibition is not due to disruption of the DNA-binding activity of the endogenous TR-RXR complex. These results suggest that inhibition of T3-stimulated transcription may be due to the sequestration of a limiting adaptor molecule(s). Hence, we hypothesize that a limiting adaptor(s), which may act as a bridging molecule between the TR-RXR complex and the basal transcriptional machinery, may be sequestered by either GST-TR beta or GST-RXR beta, resulting in the inhibition of T3-stimulated transcription.
Suen
C S
CS
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Chin
W W
WW
D000818:Animals; D002460:Cell Line; D005978:Glutathione / Q000494:pharmacology; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014284:Triiodothyronine / Q000494:pharmacology*
D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014284:Triiodothyronine; D013006:Growth Hormone; D005978:Glutathione