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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Edogenous expression of Mullerian inhibiting Substance in early postnatal rat Sertoli cells 9 requires multiple steroidogenic factor-1 and GATA-4-binding sites
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Edogenous expression of Mullerian inhibiting Substance in early postnatal rat Sertoli cells 9 requires multiple steroidogenic factor-1 and GATA-4-binding sites

机译：产后早期大鼠睾丸支持细胞9中穆勒抑制物质的内源表达需要多个类固醇生成因子1和GATA-4结合位点

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摘要

Mullerian inhibiting substance (MIS) is a key element required to complete mammalian male sex differentiation. The expression pattern of MlS is tightly regulated in fetal, neonatal. and prepu- bertal testes and adult ovaries and is well conserved among mammalian species. Although several factors have been shown to be essential to MlS expression. its regulatory mechanisms are not fully understood. We have examined MIS promoter activity in 2-day postnatal primary cultures of rat Sertoli cells that continue to express endogenous MlS mRNA. Using this system, we found that the region between human MIS-269 and - 192 is necessary for full MlS promoter activity. We identified by DNase l footprint and electrophoretic mobility-shift analyses a distal steroidogenic fac- tor-1 (SF-1)-binding site that is essential for full promoter activity. Mutational analysis of this new distal SF-1 site and the previously identified proximal SF-1 site showed that both are necessary for transcriptional activation. Moreover, the proximal promoter also contains multiple GATA-4-binding sites that are essential for func- tional promoter activity. Thus multiple SF-1- and GATA-4-binding sites in the MIS promoter are required for normal tissue-specific and developmental expression of MlS.
机译：苗勒抑制物质（MIS）是完成哺乳动物男性性别分化的关键要素。 MIS的表达模式在胎儿，新生儿中受到严格调节。以及睾丸前睾丸和成年卵巢，在哺乳动物中保存得很好。尽管已显示出几种因素对于MlS表达至关重要。其监管机制尚未完全了解。我们已经检查了大鼠Sertoli细胞在出生后两天的初次培​​养物中的MIS启动子活性，该细胞继续表达内源性MIS mRNA。使用该系统，我们发现人MIS-269和-192之间的区域对于完整的M1S启动子活性是必需的。我们通过DNase l足迹和电泳迁移率迁移分析确定了远端的类固醇生成因子1（SF-1）结合位点，这对于完整启动子活性至关重要。对这个新的远端SF-1位点和先前确定的近端SF-1位点的突变分析表明，两者都是转录激活所必需的。此外，近端启动子还包含多个GATA-4结合位点，这些位点对于功能性启动子活性至关重要。因此，MIS启动子中的多个SF-1-和GATA-4-结合位点是M1S正常组织特异性和发育表达所必需的。

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