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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alternative Splicing*
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Amino Acid Sequence
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Animals
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Base Sequence
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Blotting, Western
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COS Cells
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Cloning, Molecular
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DAX-1 Orphan Nuclear Receptor
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DNA Primers / chemistry
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DNA, Complementary / metabolism
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism*
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Dose-Response Relationship, Drug
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Exons
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HeLa Cells
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Homeodomain Proteins
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Humans
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Immunoprecipitation
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Introns
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Models, Genetic
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Molecular Sequence Data
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Plasmids / metabolism
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Polymerase Chain Reaction
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Promoter Regions, Genetic
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Protein Isoforms
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Protein Structure, Tertiary
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RNA, Messenger / metabolism
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid / chemistry*
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Receptors, Retinoic Acid / metabolism*
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Repressor Proteins / chemistry*
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Repressor Proteins / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Steroidogenic Factor 1
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Steroids / metabolism
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Tissue Distribution
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Transcription Factors / metabolism
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Transcription, Genetic
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Transfection
Substances
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DAX-1 Orphan Nuclear Receptor
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DNA Primers
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DNA, Complementary
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DNA-Binding Proteins
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Homeodomain Proteins
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NR0B1 protein, human
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NR5A1 protein, human
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Protein Isoforms
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Repressor Proteins
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Steroidogenic Factor 1
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Steroids
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Transcription Factors