KDM6B is a conserved activator at the top of the male sex determination pathway.

IF 3.7 2区生物学 Q1 DEVELOPMENTAL BIOLOGY

Development Pub Date : 2025-06-15 Epub Date: 2025-06-13 DOI:10.1242/dev.204724

Shannon M Dupont, Alexandra Garcia-Moreno, Eleanore V O'Neil, Blanche C Capel

引用次数: 0

Abstract

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.

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KDM6B是一个保守的激活因子，位于雄性性别决定通路的顶端。

在哺乳动物中，对睾丸命运的承诺由Y染色体上的Sry基因控制；然而，Sry是如何被调控的还不是很清楚。在红耳滑龟中，Dmrt1是睾丸通路的主要激活因子。通过组蛋白去甲基化酶KDM6B从Dmrt1中去除抑制组蛋白修饰H3K27me3是其激活所必需的。我们假设在哺乳动物中使用了类似的去抑制机制来激活睾丸通路。使用小鼠Kdm6b敲除模型，我们发现Kdm6b的缺失导致Sry激活和卵睾丸发育的延迟。这些结果暗示KDM6B在爬行动物和哺乳动物的性别决定级联中都是一个保守的调节器。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Development 生物-发育生物学

CiteScore

6.70

自引率

4.30%

发文量

433

审稿时长

3 months

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