SOX9 Regulates Prostaglandin D Synthase Gene Transcription in Vivo to Ensure Testis Development
| Autor: | Hirofumi Mizusaki, Yoshiakira Kanai, Dagmar Wilhelm, Ryuji Hiramatsu, Laura Widjaja, Alexander N. Combes, Peter Koopman |
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| Rok vydání: | 2007 |
| Předmět: |
Male
endocrine system Transcription Genetic Mice Transgenic SOX9 Biology Response Elements Y chromosome Biochemistry Gene Expression Regulation Enzymologic Prostaglandin-D synthase Mice chemistry.chemical_compound Y Chromosome parasitic diseases medicine Animals Cell Lineage Molecular Biology Regulation of gene expression Sertoli Cells Prostaglandin D2 High Mobility Group Proteins Gene Expression Regulation Developmental Cell Differentiation SOX9 Transcription Factor Cell Biology Sertoli cell Molecular biology Lipocalins Sex-Determining Region Y Protein Intramolecular Oxidoreductases Testis determining factor medicine.anatomical_structure chemistry biology.protein Chromatin immunoprecipitation Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 282:10553-10560 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m609578200 |
| Popis: | In mammals, male sex is determined by the Y-chromosomal gene Sry (sex-determining region of Y chromosome). The expression of Sry and subsequently Sox9 (SRY box containing gene 9) in precursors of the supporting cell lineage results in the differentiation of these cells into Sertoli cells. Sertoli cells in turn orchestrate the development of all other male-specific cell types. To ensure that Sertoli cells differentiate in sufficient numbers to induce normal testis development, the early testis produces prostaglandin D(2) (PGD(2)), which recruits cells of the supporting cell lineage to a Sertoli cell fate. Here we show that the gene encoding prostaglandin D synthase (Pgds), the enzyme that produces PGD(2), is expressed in Sertoli cells immediately after the onset of Sox9 expression. Promoter analysis in silico and in vitro identified a paired SOX/SRY binding site. Interestingly, only SOX9, and not SRY, was able to bind as a dimer to this site and transactivate the Pgds promoter. In line with this, a transgenic mouse model showed that Pgds expression is not affected by ectopic Sry expression. Finally, chromatin immunoprecipitation proved that SOX9 but not SRY binds to the Pgds promoter in vivo. |
| Databáze: | OpenAIRE |
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