The rat TSH beta gene contains distinct response elements for regulation by retinoids and thyroid hormone

被引:39
作者
Breen, JJ
Hickok, NJ
Gurr, JA
机构
[1] TEMPLE UNIV,SCH MED,FELS INST CANC RES & MOL BIOL,PHILADELPHIA,PA 19140
[2] THOMAS JEFFERSON UNIV,DEPT DERMATOL,PHILADELPHIA,PA 19107
[3] THOMAS JEFFERSON UNIV,DEPT BIOCHEM & MOL BIOL,PHILADELPHIA,PA 19107
关键词
thyroid hormone; retinoid; thyrotropin beta-subunit; gene expression; response element;
D O I
10.1016/S0303-7207(97)00099-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have previously shown that thyroid stimulating hormone-beta (TSH beta) mRNA levels are modulated by vitamin A status in vivo and using transient transfection, that suppression of rat TSH beta gene promoter activity by all-traits retinoic acid (RA) requires RA receptor (RAR) and retinoid X receptor (RXR). In this paper we have used deletion analysis to delineate the sequences of the rTSH beta gene involved in RA regulation, their relationship to the rTSH beta gene negative thyroid hormone response elements and the retinoid receptor species that interact with these sequences. Using transient transfection in CV-1 cells, we found that the -204/+9 region of the rat TSH beta gene, when fused to a luciferase reporter, was sufficient for suppression by all-trans-RA in the presence of RAR/RXR. Thus, regulation by RA did not involve the major rTSH beta negative TRE located between +15 and +43. Mutational analysis also showed that the minor rTSH beta negative TRE between -11 and +5 was not required by suppression by RA. However, in a heterologous promoter this sequence element acted as a strong positive RARE, The combination of RA and T3 treatment caused synergistic inhibition of rat TSH beta gene expression in the presence of RAR/RXR and TR. EMSA analysis demonstrated that the -204/-79 sequence binds RAR/RXR heterodimer. Therefore, we conclude that there are separate response elements for RA and T3 on the rat TSH beta gene, that the RARE binds RAR/RXR heterodimer and that RA and T3 interact functionally via these elements in the negative regulation of rat TSH beta gene expression. (C) 1997 Elsevier Science Ireland Ltd.
引用
收藏
页码:137 / 146
页数:10
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