title: Identification of a leader exon and a core promoter for the rat tuberous sclerosis 2 (Tsc2) gene and structural comparison with the human homolog.
abstract: Hereditary renal carcinoma in the Eker rat is an excellent example of predisposition to a specific cancer being transmitted as a dominant trait. Recently, we identified a germline mutation of the tuberous sclerosis 2 (Tsc2) gene in the Eker rat. In the present study, we analyzed the upstream region of the Tsc2 gene. A novel leader exon (exon 1a) in a CpG island was found, and core promoter activity was identified in a 242-bp region of this island. Exon 1a and the promoter region were conserved in the human TSC2 gene. In addition, a rat homolog of a gene found upstream of TSC2 in human has been identified, indicating that the genomic organization around Tsc2/TSC2 is conserved between the two species. Characterization of the 5' region of Tsc2 and TSC2 will facilitate studies of the regulation of the gene and its disregulation in tumorigenesis.
authors.affiliation: Department of Experimental Pathology, Cancer Institute, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Urakami
authors.forename: J P
authors.initials: JP
authors.lastname: Cheadle
authors.forename: R
authors.initials: R
authors.lastname: Aspinwall
authors.forename: P
authors.initials: P
authors.lastname: Harris
authors.forename: J R
authors.initials: JR
authors.lastname: Sampson
authors.forename: O
authors.initials: O
authors.lastname: Hino
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains / Q000235:genetics*; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection / Q000235:genetics; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D012097:Repressor Proteins; C000624653:TSC2 protein, human; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins