[Structure and function of the promoter region of the TSH receptor gene]

TSH receptor (TSHR) is expressed almost exclusively in thyroid cells. The rat TSHR gene has a TATA-less, GC-rich promoter, with multiple transcriptional start sites. The minimal promoter region, sufficient for the basal promoter activity, thyroid-specific expression and negative regulation by TSH/cAMP signal, is located between -195 and -39 bp relative to the ATG start codon, and is highly conserved in the rat and human genes. This region comprises three important elements. First, a cAMP response element (CRE), which functions as a constitutive enhancer essential for the basal promoter activity. Second, tandem repeat sequences just 5' to the CRE, which are recognized by two distinct ssDNA-binding proteins. This element suppresses the function of the CRE, thus repressing the promoter activity. Third, a binding site for the thyroid-specific transcription factor TTF-1, which dictates thyroid-specific expression and negative regulation by TSH/cAMP of the gene. Thus, the expression of the TSHR gene is exquisitely regulated by these multiple factors in thyroid and non-thyroid cells.