Temperature-dependent sex determination is mediated by pSTAT3 repression of Kdm6b
Temperature-dependent sex determination is mediated by pSTAT3 repression of Kdm6b
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DOI：
10.1126/science.aaz4165
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发表时间：
2020-04
期刊：
影响因子：
56.9
通讯作者：
C. Weber;Yingjie Zhou;Jong Gwan Lee;L. Looger;Guoying Qian;C. Ge;B. Capel
中科院分区：
文献类型：
--
作者：
C. Weber;Yingjie Zhou;Jong Gwan Lee;L. Looger;Guoying Qian;C. Ge;B. Capel
许多爬行动物的性别是由卵孵化期间巢内的温度决定的。温度调节表观遗传修饰基因Kdm6b的表达，Kdm6b负责睾丸发育。然而，温度与该因子的性别特异性表达之间的分子联系以前是未知的。Weber等人已经发现温度与Kdm6b的一个关键调节因子——信号换能器和转录激活因子3 （STAT3）的激活之间存在联系。当Ca2+在温暖的雌性生殖温度下涌入后，STAT3被磷酸化并沉默Kdm6b转录以抑制睾丸发育。阐明了高温抑制海龟雄性性别决定的分子机制。在许多爬行动物中，包括红耳滑龟（Trachemys scripta elegans），性别是由胚胎发生时的环境温度决定的。我们之前的研究表明，表观遗传调节因子Kdm6b在雄性生殖温度下升高，对激活雄性途径至关重要。在这项工作中，我们建立了温度与Kdm6b转录调控之间的因果关系。我们发现，信号转换器和转录激活因子3 （STAT3）在温暖的雌性繁殖温度下磷酸化，结合Kdm6b位点，抑制Kdm6b转录，阻断雄性途径。Ca2+的内流是STAT3磷酸化的介质，在女性温度下升高，并作为STAT3激活的温度敏感调节剂。
How egg temperature sets sex In many reptiles, sex is determined by nest temperature during egg incubation. Temperature regulates the expression of an epigenetic modifier gene called Kdm6b, which is responsible for testis development. However, the molecular connection between temperature and sex-specific expression of this factor was previously unknown. Weber et al. have identified a link between temperature and the activation of a key regulator of Kdm6b called signal transducer and activator of transcription 3 (STAT3). After an influx of Ca2+ at the warmer, female-producing temperature, STAT3 is phosphorylated and silences Kdm6b transcription to repress testis development. Science, this issue p. 303 The molecular mechanism by which high temperature inhibits male sex determination in turtles is elucidated. In many reptiles, including the red-eared slider turtle Trachemys scripta elegans (T. scripta), sex is determined by ambient temperature during embryogenesis. We previously showed that the epigenetic regulator Kdm6b is elevated at the male-producing temperature and essential to activate the male pathway. In this work, we established a causal link between temperature and transcriptional regulation of Kdm6b. We show that signal transducer and activator of transcription 3 (STAT3) is phosphorylated at the warmer, female-producing temperature, binds the Kdm6b locus, and represses Kdm6b transcription, blocking the male pathway. Influx of Ca2+, a mediator of STAT3 phosphorylation, is elevated at the female temperature and acts as a temperature-sensitive regulator of STAT3 activation.