title: Promoter analysis of the human SLC7A7 gene encoding y+L amino acid transporter-1 (y+LAT-1).
abstract: The human SLC7A7 gene on chromosome 14q11.2 encodes the y+L amino acid transporter-1 (y+LAT-1) protein that transports, together with the 4F2hc cell surface antigen, cationic amino acids through the basolateral membrane of epithelial cells in the small intestine and kidney. The SLC7A7 gene comprises 11 exons, but the first two are not translated. Mutations in the coding region of the SLC7A7 gene cause a rare autosomal disorder, lysinuric protein intolerance (LPI). We have now investigated the expression levels and putative 5' promoter elements of the SLC7A7. The 5' region of the first untranslated exon contains no TATA-box, Inr elements nor other classical promoter elements, but has instead other putative transcription factor binding sequences. The E-box and AP-2 elements were able to bind proteins in HEK293 cells and adult kidney tissue extracts, but not in fibroblasts. Using transient transfection and luciferase reporter gene studies, we showed that the first two introns located in the untranslated region contained transcriptional enhancer elements. Northern blot analysis showed low and equal SLC7A7 mRNA levels in the control and LPI patient fibroblastoid and lymphoblast cells.
authors.affiliation: Department of Medical Genetics, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520, Turku, Finland. juha.mykkanen@utu.fi
authors.forename: Juha
authors.initials: J
authors.lastname: Mykkänen
authors.forename: Minna
authors.initials: M
authors.lastname: Toivonen
authors.forename: Maaria
authors.initials: M
authors.lastname: Kleemola
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Savontaus
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.forename: Pertti
authors.initials: P
authors.lastname: Aula
authors.forename: Kirsi
authors.initials: K
authors.lastname: Huoponen
mesh_terms: D000328:Adult; D027241:Amino Acid Transport System y+L; D026905:Amino Acid Transport Systems / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics*; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection
chemical_list: D027241:Amino Acid Transport System y+L; D026905:Amino Acid Transport Systems; D027301:Fusion Regulatory Protein 1, Light Chains; D012333:RNA, Messenger; C421261:SLC7A7 protein, human; D004247:DNA; D008156:Luciferases