Dupont Shannon M, Garcia-Moreno Alexandra, O'Neil Eleanore V, Capel Blanche C
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Development. 2025 Jun 15;152(12). doi: 10.1242/dev.204724. Epub 2025 Jun 13.
In mammals, commitment to the testis fate is controlled by the gene Sry on the Y chromosome; however, how Sry is regulated is not well understood. In the red-eared slider turtle, Dmrt1 acts as the primary activator of the testis pathway. Removal of the repressive histone modification H3K27me3 from Dmrt1 by the histone demethylase KDM6B is required for its activation. We hypothesized that a similar de-repression mechanism is used in mammals to activate the testis pathway. Using a mouse knockout model for Kdm6b, we found that loss of Kdm6b leads to a delay in Sry activation and the development of an ovotestis. These results implicate KDM6B as a conserved regulator at the top of the sex determination cascade in both reptiles and mammals.
在哺乳动物中，睾丸命运的决定由Y染色体上的Sry基因控制；然而，Sry如何被调控还不太清楚。在红耳龟中，Dmrt1是睾丸发育途径的主要激活因子。组蛋白去甲基化酶KDM6B去除Dmrt1上的抑制性组蛋白修饰H3K27me3是其激活所必需的。我们推测在哺乳动物中也使用了类似的去抑制机制来激活睾丸发育途径。利用Kdm6b的小鼠基因敲除模型，我们发现Kdm6b的缺失导致Sry激活延迟和卵睾的发育。这些结果表明KDM6B是爬行动物和哺乳动物性别决定级联顶端的保守调节因子。
