Promoter cloning and characterisation of the transcriptional regulation of the human thyrostimulin A2 subunit

The novel heterodimeric glycoprotein hormone thyrostimulin consists of two unique subunits, A2 and B5. To understand its yet unknown transcriptional regulation, we characterised the 3.1-kb immediate 5′-flanking region of the human A2 gene localised on chromosome 11q13. In transient transfection assays this sequence exhibited promoter activity, which could be confined to nucleotides −506 to −347 relative to the ATG start codon. Interestingly, this minimal promoter appeared to be non-tissue-specific. Deletional, mutational and gel shift analyses revealed regulatory elements that are essential for the regulation of the A2 gene expression. Another noteworthy feature of this gene is the presence of silencer elements upstream and downstream of the promoter. To surmise, our results provide an initial step toward a detailed analysis of the underlying molecular mechanisms of the human thyrostimulin gene expression.