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Department of Developmental Biology (K.K., T.S., H.T., S.O.,
K-i.M.) National Institute for Basic Biology Department of
Molecular Biomechanics (K-i.M.) School of Life Science The
Graduate University for Advanced Studies Core Research for
Evolutional Science and Technology Japan Science and
Technology (K-i.M.) Myodaiji-cho, Okazaki 444-8585,
Japan
Third Department of Internal Medicine (K.K.,
K.O., T.Y., H.N.) Faculty of Medicine and Department of
Molecular Biology (T.S.) Graduate School of Medical Science
Kyushu University Higashi-ku, Fukuoka 812-8582
The DAX-1 (also known as AHC) gene encodes an unusual member of the nuclear hormone receptor superfamily. DAX-1 plays a critical role during gonadal and adrenal differentiation since mutations of the human DAX-1 gene cause X-linked adrenal hypoplasia congenita associated with hypogonadotropic hypogonadism. In recent studies, DAX-1 was reported to function as a transcriptional suppressor of Ad4BP/SF-1, a critical transcription factor in gonadal and adrenal differentiation. With respect to implication of Ad4BP/SF-1 in the transcriptional regulation of the DAX-1 gene, inconsistent findings have been previously reported. We investigated the upstream region of the mouse Dax-1 (also known as Ahch) gene and identified a novel Ad4/SF-1 site by transient transfection and electrophoretic mobility shift assays. In addition, immunohistochemical analyses with a specific antibody to Dax-1 indicated the presence of immunoreactive cells in steroidogenic tissues, pituitary gland, and hypothalamus. Although the distributions of Dax-1 and Ad4BP/SF-1 were very similar, they were not completely identical. The expression of Dax-1 was significantly impaired in knock-out mice of the Ftz-f1 gene, which encodes Ad4BP/SF-1. Taken together, our findings indicate that Ad4BP/SF-1 controls the transcription of the Dax-1 gene.
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