Source:http://linkedlifedata.com/resource/pubmed/id/12907682
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
43
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| pubmed:dateCreated |
2003-10-20
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| pubmed:abstractText |
Steroidogenic factor 1 (SF-1) is a transcription factor belonging to the nuclear receptor superfamily. SF-1 regulates the expression of many genes involved in reproduction, steroidogenesis, and sexual differentiation. An important SF-1 target for male sexual differentiation is the gene encoding the Müllerian-inhibiting substance hormone that induces regression of the Müllerian ducts in the developing male embryo. Not long ago, a mutation (G35E) in the human SF-1 gene was identified as the cause of sex reversal and adrenal failure in a phenotypically female but genotypically XY individual. This suggested that the mutated SF-1 protein might interfere with the expression of SF-1 target gene(s) involved in the male sexual differentiation pathway, such as MIS. Surprisingly, the initial biochemical characterization of the SF-1 G35E mutant revealed that it could bind and activate the MIS promoter as efficiently as wild-type SF-1. MIS expression, however, does not rely solely on SF-1 but rather requires the concerted action of several transcription factors including GATA-4. We have previously reported that GATA-4 and SF-1 transcriptionally cooperate to synergistically activate the MIS promoter. Thus, we hypothesized that the phenotype observed with the SF-1 G35E mutation could be explained, at least in part, by a failure and/or a disruption of GATA-4/SF-1 synergism. We found that the SF-1 G35E mutant failed to synergize with GATA-4 despite a direct physical interaction between the two proteins. Interestingly, the SF-1 G35E mutant also disrupted transcriptional synergism between wild-type SF-1 and GATA-4, indicating that it could act as a dominant negative competitor. Thus, our results strengthen the importance of a GATA-4/SF-1 cooperation for MIS transcription and reveal that disruption of this synergism might be responsible for some cases of abnormal sex differentiation in humans.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Mullerian Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fushi Tarazu Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/GATA4 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NR5A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Steroidogenic Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Testicular Hormones,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/steroidogenic factor 1, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/steroidogenic factor 1, rat
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
24
|
| pubmed:volume |
278
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
42637-42
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:12907682-Animals,
pubmed-meshheading:12907682-Anti-Mullerian Hormone,
pubmed-meshheading:12907682-Cell Line,
pubmed-meshheading:12907682-DNA-Binding Proteins,
pubmed-meshheading:12907682-Disorders of Sex Development,
pubmed-meshheading:12907682-Drug Synergism,
pubmed-meshheading:12907682-Fushi Tarazu Transcription Factors,
pubmed-meshheading:12907682-GATA4 Transcription Factor,
pubmed-meshheading:12907682-Glycoproteins,
pubmed-meshheading:12907682-Homeodomain Proteins,
pubmed-meshheading:12907682-Humans,
pubmed-meshheading:12907682-Male,
pubmed-meshheading:12907682-Mice,
pubmed-meshheading:12907682-Mutation, Missense,
pubmed-meshheading:12907682-Promoter Regions, Genetic,
pubmed-meshheading:12907682-Protein Binding,
pubmed-meshheading:12907682-Rats,
pubmed-meshheading:12907682-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12907682-Steroidogenic Factor 1,
pubmed-meshheading:12907682-Testicular Hormones,
pubmed-meshheading:12907682-Transcription, Genetic,
pubmed-meshheading:12907682-Transcription Factors,
pubmed-meshheading:12907682-Transfection
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| pubmed:year |
2003
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| pubmed:articleTitle |
A mutated form of steroidogenic factor 1 (SF-1 G35E) that causes sex reversal in humans fails to synergize with transcription factor GATA-4.
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| pubmed:affiliation |
Ontogeny-Reproduction Research Unit, CHUL Research Centre and Centre de Recherche en Biologie de la Reproduction, Department of Obstetrics and Gynecology, Université Laval, 2705 Laurier Boulevard, Sainte-Foy, Quebec G1V 4G2, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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