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

EMBO J. 1996 Dec 2;15(23):6680-90.


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 temporal- and tissue-specific pattern. To investigate the molecular mechanisms controlling the different expression patterns of the SSTRs, we cloned the 5'-flanking region of the human SSTR2 gene. Characterization of the SSTR2 promoter resulted in the identification of a novel initiator element (SSTR2inr). Transcriptional activity of the SSTR2inr is dependent on the presence of a binding site (E-box) for basic helix-loop-helix (bHLH) transcription factors. By screening a mouse brain cDNA expression 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 SSTR2inr. Furthermore, DNA binding studies demonstrate that the basal transcription factor TFIIB can be tethered to the SSTR2inr through physical interaction with SEF-2. In summary, the SSTR2inr represents a novel type 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Binding Sites
  • DNA / chemistry
  • DNA / metabolism
  • DNA Primers
  • DNA-Binding Proteins*
  • Helix-Loop-Helix Motifs
  • Humans
  • Luciferases / biosynthesis
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins*
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic*
  • Receptors, Somatostatin / biosynthesis*
  • Receptors, Somatostatin / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • TATA Box
  • TCF Transcription Factors
  • Transcription Factor 4
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA Primers
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Receptors, Somatostatin
  • Recombinant Fusion Proteins
  • TCF Transcription Factors
  • TCF4 protein, human
  • TCF7L2 protein, human
  • Tcf4 protein, mouse
  • Tcf7l2 protein, mouse
  • Transcription Factor 4
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • DNA
  • somatostatin receptor 2
  • Luciferases

Associated data

  • GENBANK/X91753