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PMID: 9590178 Published · ppublish English 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.

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

Cell ·Vol. 93 ·No. 3 ·1998-05-01 ·Pages 445-54

Nachtigal MW, Hirokawa Y, Enyeart-VanHouten DL, Flanagan JN, Hammer GD, Ingraham HA

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.

MeSH Terms

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

Chemicals

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

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Nachtigal M W

Department of Physiology, University of California at San Francisco, 94143-0444, USA.

Hirokawa Y

Enyeart-VanHouten D L

Flanagan J N

Hammer G D

Ingraham H A

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)81172-1

Published

1998-05-01

Pages

445-54

Language

English

Region

United States

NLM ID

0413066

Subset

External Links

PubMed source DOI: 10.1016/s0092-8674(00)81172-1 View journal details

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

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