title: Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci.
abstract: Fierce (frc) mice are deleted for nuclear receptor 2e1 (Nr2e1), and exhibit cerebral hypoplasia, blindness, and extreme aggression. To characterize the Nr2e1 locus, which may also contain the mouse kidney disease (kd) allele, we compared sequence from human, mouse, and the puffer fish Fugu rubripes. We identified a novel gene, c222389, containing conserved elements in noncoding regions. We also discovered a novel vertebrate gene conserved across its length in prokaryotes and invertebrates. Based on a dramatic upregulation in lactating breast, we named this gene lactation elevated-1 (LACE1). Two separate 100-bp elements within the first NR2E1 intron were virtually identical between the three species, despite an estimated 450 million years of divergent evolution. These elements represent strong candidates for functional NR2E1 regulatory elements in vertebrates. A high degree of conservation across NR2E1 combined with a lack of interspersed repeats suggests that an array of regulatory elements embedded within the gene is required for proper gene expression.
authors.affiliation: Centre for Molecular Medicine & Therapeutics, British Columbia Research Institute for Children's and Women's Health, and Department of Medical Genetics, University of British Columbia, 980 West 28(th) Avenue, Vancouver, British Columbia, V5Z 4H4, Canada.
authors.forename: Brett S
authors.initials: BS
authors.lastname: Abrahams
authors.forename: Grace M
authors.initials: GM
authors.lastname: Mak
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Berry
authors.forename: Diana L
authors.initials: DL
authors.lastname: Palmquist
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Saionz
authors.forename: Alice
authors.initials: A
authors.lastname: Tay
authors.forename: Y H
authors.initials: YH
authors.lastname: Tan
authors.forename: Sydney
authors.initials: S
authors.lastname: Brenner
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Simpson
authors.forename: Byrappa
authors.initials: B
authors.lastname: Venkatesh
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D006801:Humans; D020071:Interspersed Repetitive Sequences; D007674:Kidney Diseases / Q000235:genetics*; D051379:Mice / Q000235:genetics; D008969:Molecular Sequence Data; D057093:Orphan Nuclear Receptors; D022661:RNA, Untranslated; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D026801:Synteny; D023741:Takifugu / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C088601:NR2E1 protein, human; C490258:Nr2e1 protein, mouse; D057093:Orphan Nuclear Receptors; D022661:RNA, Untranslated; D018160:Receptors, Cytoplasmic and Nuclear