title: The genomic structure of the human UBE1L gene.
abstract: The human UBE1L gene, for which the product may well play a role in the ubiquitin system because of its high degree of identity to the ubiquitin activating enzyme, is located at 3p21, a chromosomal region consistently showing loss of heterozygosity in lung cancer. The finding that UBE1L is well expressed in normal lung tissue, but hardly or not in lung cancer-derived cell lines, prompted us to investigate its genomic structure to find an explanation for the lack of expression in lung cancer. The gene has 22 exons distributed over 8.4 kb. Both anchored PCR experiments and mapping of DNase I-hypersensitive sites point to the region immediately upstream of exon 1 as the promoter site. Three moderately to well-informative polymorphisms were found, of which one is easily directly detectable. Cancer-specific mutations were not detected. The lack of expression in lung cancer cell lines correlated with a highly decreased sensitivity towards DNAse I of the promoter region and with an almost complete methylation of the HhaI site in the first exon. 5'-Azacytidine-induced demethylation did not result in a marked increase of the UBE1L mRNA level in the tumor cell lines. This leaves the possibility that mutation or absence of yet unknown transcription factors causes a regulatory block of the UBE1L gene.
authors.affiliation: Department of Medical Genetics, University of Groningen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Kok
authors.forename: A
authors.initials: A
authors.lastname: Van den Berg
authors.forename: P M
authors.initials: PM
authors.lastname: Veldhuis
authors.forename: M
authors.initials: M
authors.lastname: Franke
authors.forename: P
authors.initials: P
authors.lastname: Terpstra
authors.forename: C H
authors.initials: CH
authors.lastname: Buys
mesh_terms: D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D008025:Ligases / Q000737:chemistry / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008745:Methylation; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D044764:Ubiquitin-Activating Enzymes; D044767:Ubiquitin-Protein Ligases
chemical_list: D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D044764:Ubiquitin-Activating Enzymes