Cloning and functional analysis of SEL1L promoter region, a pancreas-specific gene

We examined the promoter activity of SEL1L, the human ortholog of the C, el egans gene sel-1, a negative regulator of LIN-12/NOTCH receptor proteins. T o understand the relation in SEL1L transcription pattern observed in differ ent epithelial cells, we determined the transcription start site and sequen ced the 5' flanking region. Sequence analysis revealed the presence of cons ensus promoter elements-CC boxes and a CAAT box-but the absence of a TATA m otif, Potential binding sites for transcription factors that are involved i n tissue-specific gene expression were identified, including: activator pro tein-2 (AP-2), hepatocyte nuclear factor-3 (HNF3 beta), homeobox Nkx2-5 and GATA-1. Transcription activity of the TATA-less SEL1L promoter was analyzed by tran sient transfection using luciferase reporter gene constructs. A core basal promoter of 302 bp was sufficient for constitutive promoter activity in all the cell types studied. This genomic fragment contains a CAAT and several GC boxes. The activity of the SEL1L promoter was considerably higher in mou se pancreatic beta cells (beta TC3) than in several human pancreatic neopla stic cell lines; an even greater reduction of its activity was observed in cells of nonpancreatic origin. These results suggest that SEL1L promoter ma y be a useful tool in gene therapy applications for pancreatic pathologies.