Abstract
Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that bind to thyroid hormone response elements (TREs) to mediate positive and negative regulation of transcription of thyroid hormone-responsive genes. TR binding to TREs can be enhanced by interaction with a nuclear protein, triiodothyronine (T3) receptor auxiliary protein (TRAP). There are two major isoforms of thyroid hormone receptors, TR alpha-1 and TR beta-1, which are encoded on two separate genes. We studied the binding of TR alpha-1 and TR beta-1 to several TREs: the chick lysozyme TRE (F2), which is positively regulated by T3; rabbit beta-myosin heavy chain TRE, which is negatively regulated by T3; and an idealized inverted palindrome, TRElap. We demonstrate the formation of homodimers, TR alpha/TR beta dimers, and TR/TRAP heterodimers when receptor is bound to these DNA sequences. Surprisingly, we found that T3 decreased TR alpha-1 and TR beta-1 homodimer binding in a dose-dependent manner to these TREs as well as TR alpha/TR beta dimer binding to F2. In contrast, T3 did not affect TR/TRAP heterodimer binding to TREs suggesting that this heterodimer may be the stable complex occupying TREs in the presence of ligand.
Highlights
Disease, Departmentof Medicine, University of Alabama at Birmingham, Birmingham, Alabama35294 tein (TRAP), thaetnhances Thyroid hormone receptors (TRs) binding to thyroid hormone responseelements (TREs)[17,20,21,22,23]
Given these multiple potential receptor complexes, it is not known which complexes predominate when receptors are bound to TREs, and in particular, what effect thyroid hormone has on the formation of these complexes
We studied the binding of TRa-1 and TRp-1 to several TREs: the chick lysozyme TRE(F2), which is positively regulated by T3 [25]; rabbit P-myosin heavy chain TRE, which is negatively regulated by TO[26, 27]’; and an idealized inverted palindrome, TREI, [25] using electrophoretic mobility shift assay (EMSA)
Summary
Departmentof Medicine, University of Alabama at Birmingham, Birmingham, Alabama35294 tein (TRAP), thaetnhances TR binding to TREs[17,20,21,22,23]. Since this protein is present in nuclear extracts from many different tissues and species [17, 21], receptor/TRAP heterodimers potentiallycan be formed in all cells that contain TRs. Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that bind to thyroid hormone responseelements (TREs) to mediate positive and negative regulation of transcription of thyroid hormone-responsive genes. Myosin heavy chain TRE, which is negatively regu- Surprisingly, we found that thyroid hormone decreased TRalated by T3; and an idealized inverted palindrome, 1and TRp-1homodimer binding in a dose-dependent manner
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