Conserved regulatory modules in the Sox9 testis-specific enhancer predict roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination
Conserved regulatory modules in the Sox9 testis-specific enhancer predict roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination
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DOI：
10.1016/j.biocel.2009.07.001
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Harley, Vincent R.
中科院分区：
文献类型：
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作者：
Bagheri-Fam, Stefan;Sinclair, Andrew H.;Harley, Vincent R.
虽然脊椎动物物种之间的主要性别决定开关不同，但睾丸发育中的关键下游事件，即Sox 9的雄性特异性上调，是保守的。到目前为止，只有两个性别决定开关基因已被确定，在哺乳动物和Dmrt 1相关基因Dmy（Dmrt 1bY）青鳉鱼中的Sty。对小鼠Sox 9的表达明显被SRY上调，并由SOX 9维持，两者都直接激活Sox 9的核心1.3kb睾丸特异性增强子（TESCO）。目前尚不清楚Sox 9表达如何在没有Sry的物种（即非哺乳动物物种）中上调和维持。在这项研究中，我们进行了深入的比较基因组学方法，并表明TESCO包含一个180 bp的进化保守区（ECR），该区域存在于有袋动物，单孔目动物，鸟类，爬行动物和两栖动物中。ECR包含高度保守的模块，其预测SOX、TCF/LEF、Forkhead、DMRT和加塔蛋白在脊椎动物性别决定/分化中的调节作用。我们的数据表明，四足动物在睾丸中Sox 9调控方面有共同之处，尽管它们具有不同的性别决定开关机制。他们还表明，Sox 9自动调节是所有四足动物共有的一种古老机制，这提高了哺乳动物中SRY通过模仿这种调节而进化的可能性。ECR调控序列的验证将为脊椎动物性别决定提供新的视角。(C)2009爱思唯尔有限公司保留所有权利。
While the primary sex determining switch varies between vertebrate species, a key downstream event in testicular development, namely the male-specific up-regulation of Sox9, is conserved. To date, only two sex determining switch genes have been identified, Sty in mammals and the Dmrt1-related gene Dmy (Dmrt1bY) in the medaka fish Oryzias latipes. In mice. Sox9 expression is evidently up-regulated by SRY and maintained by SOX9 both of which directly activate the core 1.3 kb testis-specific enhancer of Sox9 (TESCO). How Sox9 expression is up-regulated and maintained in species without Sry (i.e. non-mammalian species) is not understood. In this study, we have undertaken an in-depth comparative genomics approach and show that TESCO contains an evolutionarily conserved region (ECR) of 180 bp which is present in marsupials, monotremes, birds, reptiles and amphibians. The ECR contains highly conserved modules that predict regulatory roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination/differentiation. Our data suggest that tetrapods share common aspects of Sox9 regulation in the testis, despite having different sex determining switch mechanisms. They also suggest that Sox9 autoregulation is an ancient mechanism shared by all tetrapods, raising the possibility that in mammals, SRY evolved by mimicking this regulation. The validation of ECR regulatory sequences conserved from human to frogs will provide new insights into vertebrate sex determination. (C) 2009 Elsevier Ltd. All rights reserved.