SOX9 Regulates Prostaglandin D Synthase Gene Transcription in Vivo to Ensure Testis Development*
SOX9 Regulates Prostaglandin D Synthase Gene Transcription in Vivo to Ensure Testis Development*
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DOI：
10.1074/jbc.m609578200
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发表时间：
2007-04
影响因子：
4.8
通讯作者：
D. Wilhelm;R. Hiramatsu;H. Mizusaki;Laura Widjaja;A. Combes;Yoshiakira Kanai;P. Koopman
中科院分区：
文献类型：
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作者：
D. Wilhelm;R. Hiramatsu;H. Mizusaki;Laura Widjaja;A. Combes;Yoshiakira Kanai;P. Koopman
在哺乳动物中，男性性别是由Y染色体基因Sry（Y染色体的性别决定区）决定的。在支持细胞谱系的前体中Sry和随后Sox 9（含有SRY盒的基因9）的表达导致这些细胞分化成支持细胞。支持细胞反过来协调所有其他男性特异性细胞类型的发育。为了确保支持细胞分化足够数量以诱导正常睾丸发育，早期睾丸产生前列腺素D2（PGD 2），其将支持细胞谱系的细胞募集到支持细胞命运。在这里，我们表明，基因编码的前列腺素D合酶（Pgds），产生PGD 2的酶，表达在支持细胞Sox 9表达的发病后立即。启动子分析在电脑和体外确定了一对SOX/SRY结合位点。有趣的是，只有SOX 9而不是SRY能够作为二聚体结合到该位点并反式激活Pgds启动子。与此一致，转基因小鼠模型显示Pgds表达不受异位Sry表达的影响。最后，染色质免疫沉淀证明SOX 9而不是SRY在体内与Pgds启动子结合。
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 D2 (PGD2), 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 PGD2, 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.