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PLoS Genet.:揭示鱼类中温度与性别的表观遗传学机制

  1. 性别决定
  2. 温度
  3. 甲基化
  4. 芳香化酶
  5. 表观遗传学

来源:生物谷 2011-12-31 10:05

12月29日,据《每日科学》报道,一项由西班牙国家研究委员会(CSIC)海洋科学研究所领导、基因组调控中心(CRG)研究人员共同合作的研究,发现了鱼类中温度和性腺性别之间的表观遗传学机制。在雌鱼中,高温会增加性腺芳香酶启动子的DNA甲基化。 环境温度对性别决定有影响。有些物种,如大西洋银边鱼,其性别决定主要取决于温度。

12月29日,据《每日科学》报道,一项由西班牙国家研究委员会(CSIC)海洋科学研究所领导、基因组调控中心(CRG)研究人员共同合作的研究,发现了鱼类中温度和性腺性别之间的表观遗传学机制。在雌鱼中,高温会增加性腺芳香酶启动子的DNA甲基化。

环境温度对性别决定有影响。有些物种,如大西洋银边鱼,其性别决定主要取决于温度。而另外一些物种,其性别决定已写在其DNA内,但温度仍然能够颠覆这种遗传"指令"。

之前有关欧洲鲈鱼(一种鱼,其性别决定取决于遗传因素和环境因素的共同作用)的研究表明,从一个正常性别比例的群体开始--即等比例的雄性和磁性个体,只需要在早期发育的一个关键时期通过增加水温,即可得到一个全是雄性个体的群体。

最有趣的现象是,温度在性腺未分化的某个时刻影响最大,而不是性腺开始形成。为什么会发生这种情况,是什么使温度能颠覆遗传因素,至今,都是个由来已久的难题。

现在,一项由西班牙国家研究委员会(CSIC)领导的研究解开了谜底。由巴塞罗那CSIC海洋科学研究所Francesc Piferrer教授领导的团队,描述了由温度升高诱导触发芳香化酶基因沉默的机制。

芳香化酶是一种能将雄激素转变为雌激素的酶,它在所有非哺乳类脊椎动物卵巢发育中至关重要。如果没有芳香化酶,就不会有雌激素;没有雌激素,卵巢就不可能发育。这项研究,将发表于本期PLoS遗传学期刊上。

早期效应

在实验中,科学家将2组欧洲鲈鱼幼鱼在它们生命的第一周培养在不同的温度(常温和高温)中。

结果表明,高温增加了芳香化酶启动子(cyp19a)的DNA甲基化,这反过来又驱动了它的沉默,因为其转录活性被抑制了。暴露于高温的这组,那些基因上是雌性只部分的受了影响的雌鱼,最终仍发育为雌性。然而,还有其他一些基因上是雌性但含有高水平的DNA甲基化的雌鱼,最终发育成了雄性,因为它们的芳香化酶被抑制了。

这是第一次,表观遗传学机制将环境因素与性别决定的细胞内机制联系在一起,而后者已在任何动物中被描述过。在此之前,只有一个类似的机制在一些植物中被描述过。

如研究员Francesc Piferrer指出,动物受影响非常快,远在组织学样本中出现可见性的雌雄差异(这发生在生命的第150天)之前,甚至远在性腺开始形成(这发生在生命的第35天)之前。

这项工作解释了,为什么水温仅升高几度就能将这些动物男性化,

它同样解释了,为什么许多在农场养殖的鱼是雄性,因为农民在幼鱼期升高了水温以加速它们的成长。Piferrer补充道,温度控制性别决定在爬行动物中非常常见。如果在这类脊椎动物中也存在一个类似的机制,那将是非常有意思的一件事。(生物谷bioon.com)

DNA Methylation of the Gonadal Aromatase (cyp19a) Promoter Is Involved in Temperature-Dependent Sex Ratio Shifts in the European Sea Bass.

Navarro-Martín L, Viñas J, Ribas L, Díaz N, Gutiérrez A, et al.

Abstract :Sex ratio shifts in response to temperature are common in fish and reptiles. However, the mechanism linking temperature during early development and sex ratios has remained elusive. We show in the European sea bass (sb), a fish in which temperature effects on sex ratios are maximal before the gonads form, that juvenile males have double the DNA methylation levels of females in the promoter of gonadal aromatase (cyp19a), the enzyme that converts androgens into estrogens. Exposure to high temperature increased the cyp19a promoter methylation levels of females, indicating that induced-masculinization involves DNA methylation-mediated control of aromatase gene expression, with an observed inverse relationship between methylation levels and expression. Although different CpGs within the sb cyp19a promoter exhibited different sensitivity to temperature, we show that the increased methylation of the sbcyp19a promoter, which occurs in the gonads but not in the brain, is not a generalized effect of temperature. Importantly, these effects were also observed in sexually undifferentiated fish and were not altered by estrogen treatment. Thus, methylation of the sb cyp19a promoter is the cause of the lower expression of cyp19a in temperature-masculinized fish. In vitro, induced methylation of the sb cyp19a promoter suppressed the ability of SF-1 and Foxl2 to stimulate transcription. Finally, a CpG differentially methylated by temperature and adjacent to a Sox transcription factor binding site is conserved across species. Thus, DNA methylation of the aromatase promoter may be an essential component of the long-sought-after mechanism connecting environmental temperature and sex ratios in vertebrate species with temperature-dependent sex determination.

 Author Summary :Temperature changes during early embryonic and/or larval stages are able to modify sex ratios in fish and reptiles. However, the underlying mechanism by which temperature is able to modify the molecular pathways that developing gonads follow to become ovaries or testes is still unknown. One of the most interesting questions raised from previous studies with our model species, the European sea bass, was how temperature could affect the developmental fate of the gonads at a time when they were not even formed in the most rudimentary manner. This was the telltale sign of an epigenetic mechanism. In this study, DNA methylation levels of the aromatase promoter were analyzed in European sea bass exposed to different temperatures during early developmental stages. Aromatase is the enzyme that converts androgens (male hormones) into estrogens (female hormones), which are essential for ovarian development in all non-mammalian vertebrates. We show that increased temperature during a critical period in early development is able to increase DNA methylation of the aromatase promoter, preventing aromatase gene expression. We conclude that gonadal aromatase promoter methylation is most likely part of the long-sought-after mechanism connecting temperature and environmental sex determination in vertebrates.

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