Abstract

Effects of human retinoid X receptor α (hRXRα) and its ligand, 9- cis-retinoic acid, on T 3-mediated auto-regulation of hTRβ1 gene expression were examined using a chloramphenicol acetyltransferase (CAT) reporter system, and a deletional analysis of the promoter. hRXRα enhanced T 3-dependent CAT induction mediated through the proximal (p) TRE in a ligand (9- cis-retinoic acid) independent manner. In a gel mobility shift assay, hRXRα enhanced the binding of hTRβ1 to the pTRE by the formation of hRXRα-hTRβ1 heterodimers. On the other hand, hRXRα and 9- cis-retinoic acid did not show any effects on T 3-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 T 3 independent suppresser effect on the function of the pTRE and dTRE. Thus, this region may be an important regulator of the T 3 dependent up-regulation of the TRβ1 gene expression which is observed only under specific conditions.

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