title: Allelic polymorphisms in the transcriptional regulatory region of human SEL1L.
abstract: In this work, we explored the existence of genetic variants within the SEL1L transcriptional regulatory region by direct sequencing of the basal promoter. SEL1L is the human ortholog of the Caenorhabditis elegans gene sel-1, a negative regulator of LIN-12/NOTCH receptor proteins. To understand the relation in SEL1L transcription pattern observed in different epithelial cells, we analysed its promoter activity. We found it to be considerably higher only in pancreatic cells. We then looked for the presence of genetic variability within this region by sequencing the minimal promoter of 63 individuals (126 alleles); two new and associated polymorphic variants were found only in few lung carcinoma bearing patients. The functional effects of this polymorphism was analysed by transient transfection assay which resulted in a significant increase in the transcriptional activity of the gene.
authors.affiliation: Institute of Advanced Biomedical Technologies, National Research Council, Via Fratelli Cervi 93, Segrate, 20090, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cattaneo
authors.forename: M
authors.initials: M
authors.lastname: Zollo
authors.forename: G
authors.initials: G
authors.lastname: Malferrari
authors.forename: R
authors.initials: R
authors.lastname: Orlandi
authors.forename: A
authors.initials: A
authors.lastname: D'Angelo
authors.forename: S
authors.initials: S
authors.lastname: Menard
authors.forename: I
authors.initials: I
authors.lastname: Biunno
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010179:Pancreas / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; C117384:SEL1L protein, human; C492169:Sel1h protein, mouse