Overexpression of Kdm6b induces testicular differentiation in a temperature-dependent sex determination system

Kdm6b 的过度表达在温度依赖性性别决定系统中诱导睾丸分化

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作者:Qiran Chen, Wei Sun, Lin Jin, Yingjie Zhou, Fang Li, Chutian Ge

Abstract

Abstract in English, Chinese In reptiles, such as the red-eared slider turtle ( Trachemys scripta elegans), gonadal sex determination is highly dependent on the environmental temperature during embryonic stages. This complex process, which leads to differentiation into either testes or ovaries, is governed by the finely tuned expression of upstream genes, notably the testis-promoting gene Dmrt1 and the ovary-promoting gene Foxl2. Recent studies have identified epigenetic regulation as a crucial factor in testis development, with the H3K27me3 demethylase KDM6B being essential for Dmrt1 expression in T. s. elegans. However, whether KDM6B alone can induce testicular differentiation remains unclear. In this study, we found that overexpression of Kdm6b in T. s. elegans embryos induced the male development pathway, accompanied by a rapid increase in the gonadal expression of Dmrt1 at 31°C, a temperature typically resulting in female development. Notably, this sex reversal could be entirely rescued by Dmrt1 knockdown. These findings demonstrate that Kdm6b is sufficient for commitment to the male pathway, underscoring its role as a critical epigenetic regulator in the sex determination of the red-eared slider turtle. 许多爬行动物(如红耳龟)的性别取决于胚胎发育的环境温度。该性别决定过程涉及一系列上游基因如促睾丸分化的 Dmrt1及促卵巢分化的 Foxl2的精细调控。作者前期研究表明,组蛋白去甲基化酶KDM6B的表达是直接激活 Dmrt1转录的必要条件。然而,KDM6B是否能单独诱导睾丸分化尚不清楚。在该研究中,我们发现在产雌温度下对红耳龟胚胎进行 Kdm6b过表达会迅速上调性腺中 Dmrt1的表达,并诱导性腺分化为睾丸。此外,敲低 Dmrt1能够阻断 Kdm6b过表达导致的雌向雄性逆转过程,性腺最终仍发育成卵巢。实验结果表明 Kdm6b通过上调 Dmrt1使性腺发育成睾丸。因此,KDM6B是红耳龟性别决定过程中的关键表观遗传调控因子。.

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