Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.

Abstract	Products of steroidogenic factor 1 (SF-1) and Wilms' tumor 1 (WT1) genes are essential for mammalian gonadogenesis prior to sexual differentiation. In males, SF-1 participates in sexual development by regulating expression of the polypeptide hormone Müllerian inhibiting substance (MIS). Here, we show that WT1 -KTS isoforms associate and synergize with SF-1 to promote MIS expression. In contrast, WT1 missense mutations, associated with male pseudohermaphroditism in Denys-Drash syndrome, fail to synergize with SF-1. Additionally, the X-linked, candidate dosage-sensitive sex-reversal gene, Dax-1, antagonizes synergy between SF-1 and WT1, most likely through a direct interaction with SF-1. We propose that WT1 and Dax-1 functionally oppose each other in testis development by modulating SF-1-mediated transactivation.
Authors	M W Nachtigal, Y Hirokawa, D L Enyeart-VanHouten, J N Flanagan, G D Hammer, H A Ingraham
Journal	Cell (Cell) Vol. 93 Issue 3 Pg. 445-54 (May 01 1998) ISSN: 0092-8674 [Print] United States
PMID	9590178 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References	DAX-1 Orphan Nuclear Receptor DNA-Binding Proteins Fushi Tarazu Transcription Factors Glycoproteins Growth Inhibitors Homeodomain Proteins NR0B1 protein, human NR5A1 protein, human Nr0b1 protein, rat RNA, Messenger Receptors, Cytoplasmic and Nuclear Receptors, Retinoic Acid Repressor Proteins Steroidogenic Factor 1 Testicular Hormones Transcription Factors WT1 Proteins steroidogenic factor 1, rat Anti-Mullerian Hormone DNA
Topics	Animals Anti-Mullerian Hormone Cell Line DAX-1 Orphan Nuclear Receptor DNA (metabolism) DNA-Binding Proteins (analysis, genetics, metabolism, physiology) Disorders of Sex Development (genetics) Female Fushi Tarazu Transcription Factors Gene Expression Regulation, Developmental (genetics) Genes, Wilms Tumor (physiology) Glycoproteins Growth Inhibitors (genetics) Homeodomain Proteins Humans Male Models, Genetic Mutation Organ Specificity Ovary (chemistry, embryology) Placenta (cytology) RNA, Messenger (analysis) Rats Receptors, Cytoplasmic and Nuclear Receptors, Retinoic Acid (genetics, metabolism, physiology) Repressor Proteins Sex Determination Processes Steroidogenic Factor 1 Testicular Hormones (genetics) Testis (chemistry, embryology) Transcription Factors (analysis, genetics, metabolism, physiology) Transcriptional Activation (genetics) WT1 Proteins

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