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
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
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DOI：
10.1210/me.2003-0176
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发表时间：
2004-06-01
影响因子：
--
通讯作者：
Saunders, GF
中科院分区：
文献类型：
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作者：
Hossain, A;Li, C;Saunders, GF
DAX-1（X染色体基因1上的剂量敏感性性逆转-肾上腺发育不良先天性关键区域; NR 0 B1）是一种孤儿核受体，在肾上腺和下丘脑-垂体性腺轴的发育和功能中起重要作用。DAX-1蛋白充当参与类固醇生成途径的基因的转录阻遏物。我们已经确定了一个新的异构体编码的DAX-1的已知外显子1和以前未识别的外显子（外显子2alpha），位于DAX-1的内含子1。这种新的转录本，我们命名为DAX-1 α，终止于外显子2 α;外显子2编码的C-末端阻遏物结构域的最后70个氨基酸缺失。DAX-1 α编码401个氨基酸的蛋白质;前389个氨基酸由外显子1编码，最后12个由外显子2 α编码。使用常规RT-PCR和实时RT-PCR分析，我们发现DAX-1 α在肾上腺、脑、肾、卵巢和睾丸中大量表达。我们还发现，DAX-1 α可以结合类固醇生成因子1和DNA，但不能抑制类固醇生成因子1介导的报告基因的转录激活，并在某些条件下作为DAX-1的拮抗剂。
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.