The Sex-Determining Factors SRY and SOX9 Regulate Similar Target Genes and Promote Testis Cord Formation during Testicular Differentiation
The Sex-Determining Factors SRY and SOX9 Regulate Similar Target Genes and Promote Testis Cord Formation during Testicular Differentiation
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DOI：
10.1016/j.celrep.2014.06.055
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发表时间：
2014-08-07
期刊：
影响因子：
8.8
通讯作者：
Lau, Yun-Fai Chris
中科院分区：
文献类型：
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作者：
Li, Yunmin;Zheng, Ming;Lau, Yun-Fai Chris
男性性别决定由性别决定区 Y (SRY) 和相关的 SRY-box 9 (SOX9) 转录因子依次介导。为了了解 SRY 和 SOX9 的基因调控层次结构，在性别决定时对小鼠性腺细胞进行了一系列染色质免疫沉淀和全基因组启动子平铺微阵列 (ChIP-Chip) 实验。 SRY 和 SOX9 与参与睾丸分化的许多常见靶标的启动子结合，并调节它们在支持细胞中的表达。 SRY 与多种卵巢分化基因结合，并通过 WNT/β-连环蛋白信号传导抑制其激活。支持细胞-支持细胞连接信号传导对于睾丸索的形成很重要，是 SRY 和 SOX9 靶标中最重要的经典通路。因此，SRY通过抑制卵巢和激活睾丸分化基因来决定支持细胞的命运，促进早期支持细胞形成睾丸索，然后将其功能传递给SOX9，SOX9在性别决定方面除了SRY作用外，还调节共同目标并激活其自身的基因调控程序。
Male sex determination is mediated sequentially by sex-determining region Y (SRY) and related SRY-box 9 (SOX9) transcription factors. To understand the gene regulatory hierarchy for SRY and SOX9, a series of chromatin immunoprecipitation and whole-genome promoter tiling microarray (ChIP-Chip) experiments were conducted with mouse gonadal cells at the time of sex determination. SRY and SOX9 bind to the promoters of many common targets involved in testis differentiation and regulate their expression in Sertoli cells. SRY binds to various ovarian differentiation genes and represses their activation through WNT/beta-catenin signaling. Sertoli cell-Sertoli cell junction signaling, important for testis cord formation, is the top canonical pathway among the SRY and SOX9 targets. Hence, SRY determines Sertoli cell fate by repressing ovarian and activating testicular differentiation genes, promotes early Sertoli cells to form testis cord, and then passes on its functions to SOX9, which regulates common targets and activates its own gene regulatory program, beyond SRY actions, in sex determination.