THE HELIX-LOOP-HELIX TRANSCRIPTION FACTOR SEF-2 REGULATES THE ACTIVITY OF A NOVEL INITIATOR ELEMENT IN THE PROMOTER OF THE HUMAN SOMATOSTATIN RECEPTOR-II GENE

The effects of somatostatin hormones are mediated by a family of five different seven-helix transmembrane spanning receptors (SSTR1-5), The expression of the five different SSTR subtypes displays a complex temp oral- and tissue-specific pattern, To investigate the molecular mechan isms controlling the different expression patterns of the SSTRs, we cl oned the 5'-flanking region of the human SSTR2 gene, Characterization of the SSTR2 promoter resulted in the identification of a novel initia tor element (SSTR2inr). Transcriptional activity of the SSTR2inr is de pendent on the presence of a binding site (E-box) for basic helix-loop -helix (bHLH) transcription factors, By screening a mouse brain cDNA e xpression library we isolated a cDNA coding for the bHLH transcription factor SEF-2, SEF-2 binds to the E-box present in the SSTR2inr, both in vitro and in vivo and activates transcription from the SSTR2inr. A single point mutation within the E-box eliminates binding of SEF-2 and results in a complete loss of transcriptional activity of the SSTR2in r, Furthermore, DNA binding studies demonstrate that the basal transcr iption factor TFIIB can be tethered to the SSTR2inr through physical i nteraction with SEF-2, In summary, the SSTR2inr represents a novel typ e of initiator element that confers gene expression in the absence of a TATA-box or binding sites for other known initiator factors, like YY -1 or USF.