Sox9 regulation during sex determination Sex determination is regulated by the Sox9 gene. During testis differentiation, this gene is directly targeted by the product of the Y chromosome–encoded gene Sry. The regulatory region of Sox9 is complex, which is typical of genes with multiple roles in development. Gonen et al. find that a single far-upstream 557–base pair element is critical for up-regulating Sox9. Without it, XY mice develop as females instead of males. The 557–base pair enhancer is conserved, likely to be relevant to human disorders of sex differentiation, and probably essential because it acts early in a time-critical process, and any failure allows ovary-specific factors to dominate. Science, this issue p. 1469 A single early-acting enhancer within a complex regulatory region is crucial for the role of Sox9 in testis determination. Cell fate decisions require appropriate regulation of key genes. Sox9, a direct target of SRY, is pivotal in mammalian sex determination. In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of Sox9. Although others are redundant, enhancer 13 (Enh13), a 557–base pair element located 565 kilobases 5′ from the transcriptional start site, is essential to initiate mouse testis development; its deletion results in XY females with Sox9 transcript levels equivalent to those in XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans.

中文翻译：

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Sox9 的单个远端增强子缺失后的性别逆转

性别决定过程中的 Sox9 调控 性别决定由 Sox9 基因调控。在睾丸分化过程中，该基因被 Y 染色体编码基因 Sry 的产物直接靶向。Sox9 的调控区域是复杂的，这是在发育中具有多种作用的基因的典型特征。戈南等人。发现单个远上游 557 碱基对元件对于上调 Sox9 至关重要。没有它，XY 小鼠会发育成雌性而不是雄性。557 个碱基对增强子是保守的，可能与人类性别分化障碍有关，并且可能是必不可少的，因为它在时间关键过程的早期起作用，并且任何失败都会使卵巢特异性因素占主导地位。科学，本期第 3 页。1469 复杂调节区域内的单一早期作用增强剂对于 Sox9 在睾丸测定中的作用至关重要。细胞命运决定需要适当调节关键基因。Sox9 是 SRY 的直接目标，在哺乳动物性别决定中至关重要。体内高通量染色质可及性技术、转基因测定和基因组编辑揭示了 Sox9 上游 2 兆碱基基因沙漠中的几种新的性腺调节元件。尽管其他是多余的，但增强子 13 (Enh13) 是一个 557 个碱基对元件，位于转录起始位点 5' 565 kb 处，对于启动小鼠睾丸发育至关重要。它的缺失导致 XY 雌性的 Sox9 转录水平与 XX 性腺中的水平相当。我们的数据与 SRY 的时间敏感活动一致，并表明增强剂使用的严格顺序。Enh13 是保守的并嵌入在一个 32.5 千碱基的区域内，该区域在人类中的缺失与 XY 性逆转有关，