title: Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing.
abstract: DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1; NR0B1) is an orphan nuclear receptor that plays an important role in the development and functioning of the adrenal gland and hypothalamic-pituitary gonadal axis. The DAX-1 protein acts as a transcriptional repressor of genes involved in the steroidogenic pathway. We have identified a novel isoform encoded by the known exon 1 of DAX-1 and a previously unrecognized exon (exon 2alpha) that lies within intron 1 of DAX-1. This novel transcript, which we designated DAX-1alpha, is terminated at exon 2alpha; the last 70 amino acids of the C-terminal repressor domain encoded by exon 2 are absent. DAX-1alpha encodes a protein of 401 amino acids; the first 389 amino acids are encoded by exon 1 and the last 12 are encoded by exon 2alpha. Using conventional RT-PCR and real-time RT-PCR analyses, we found that DAX-1alpha is abundantly expressed in the adrenal gland, brain, kidney, ovary, and testis. We also found that DAX-1alpha can bind to steroidogenic factor 1 and to DNA but is unable to repress steroidogenic factor 1-mediated transcriptional activation of the reporter gene and acts as an antagonist of DAX-1 under certain conditions.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030-4009, USA.
authors.forename: Anwar
authors.initials: A
authors.lastname: Hossain
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Grady F
authors.initials: GF
authors.lastname: Saunders
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D003001:Cloning, Molecular; D057137:DAX-1 Orphan Nuclear Receptor; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005091:Exons; D006367:HeLa Cells; D018398:Homeodomain Proteins; D006801:Humans; D047468:Immunoprecipitation; D007438:Introns; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054339:Steroidogenic Factor 1; D013256:Steroids / Q000378:metabolism; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C539965:NR0B1 protein, human; C515057:NR5A1 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D013256:Steroids; D014157:Transcription Factors