TY - JOUR
T1 - 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
AU - Hossain, Anwar
AU - Li, Chun
AU - Saunders, Grady F.
PY - 2004/6
Y1 - 2004/6
N2 - DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1; NROB1) 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 2α) that lies within intron 1 of DAX-1. This novel transcript, which we designated DAX-1α, is terminated at exon 2α; the last 70 amino acids of the C-terminal repressor domain encoded by exon 2 are absent. DAX-1α 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 2α. Using conventional RT-PCR and real-time RT-PCR analyses, we found that DAX-1α is abundantly expressed in the adrenal gland, brain, kidney, ovary, and testis. We also found that DAX-1α 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.
AB - DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1; NROB1) 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 2α) that lies within intron 1 of DAX-1. This novel transcript, which we designated DAX-1α, is terminated at exon 2α; the last 70 amino acids of the C-terminal repressor domain encoded by exon 2 are absent. DAX-1α 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 2α. Using conventional RT-PCR and real-time RT-PCR analyses, we found that DAX-1α is abundantly expressed in the adrenal gland, brain, kidney, ovary, and testis. We also found that DAX-1α 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.
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U2 - 10.1210/me.2003-0176
DO - 10.1210/me.2003-0176
M3 - Article
C2 - 15044589
AN - SCOPUS:2542448014
SN - 0888-8809
VL - 18
SP - 1428
EP - 1437
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 6
ER -