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Transcriptional regulation of human thyroid hormone receptor β1 gene expression: effect of human retinoid X receptor and identification of a transcriptional silencer region |
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| Authors: | Akihiro Sakurai Satoru Suzuki Miyuki Katai Takahide Miyamoto Hiroaki Kobayashi Koji Nakajima Kazuo Ichikawa Leslie J. DeGroot Kiyoshi Hashizume |
| Affiliation: | a Department of Geriatrics, Endocrinology and Metabolism, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390, Japan b Thyroid Study Unit, The University of Chicago, Chicago, IL 60637, USA |
| Abstract: | Effects of human retinoid X receptor (hRXR) and its ligand, 9-cis-retinoic acid, on T3-mediated auto-regulation of hTRβ1 gene expression were examined using a chloramphenicol acetyltransferase (CAT) reporter system, and a deletional analysis of the promoter. hRXR enhanced T3-dependent CAT induction mediated through the proximal (p) TRE in a ligand (9-cis-retinoic acid) independent manner. In a gel mobility shift assay, hRXR enhanced the binding of hTRβ1 to the pTRE by the formation of hRXR-hTRβ1 heterodimers. On the other hand, hRXR and 9-cis-retinoic acid did not show any effects on T3-dependent CAT induction mediated through the distal (d) TRE or the binding of hTRβ1 to the dTRE. A four hundred-base pair (bp) fragment adjacent upstream of the dTRE showed a T3 independent suppresser effect on the function of the pTRE and dTRE. Thus, this region may be an important regulator of the T3 dependent up-regulation of the TRβ1 gene expression which is observed only under specific conditions. |
| Keywords: | Thyroid hormone receptor Retinoid X receptor Chloramphenicol acetyltransferase assay Gel mobility shift assay Gene expression |
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