温度可以调控鱼类性别的表观遗传学机制（DNA甲基化）

Tlexander

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3 ?9 f  N) b9 F; G! Y3 E  K1 v关键点：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
9 ]* V- V4 y) Y# o! I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。
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* N0 z9 a8 q7 Z4 u# z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。' p, d" d) _0 t+ \2 F7 C

. S6 s8 `$ ]0 j7 \5 h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。
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, C3 T2 z& x( P: ^: p9 z5 [4 y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。
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: g% [5 b- ^2 M1 d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+ W$ a  R2 S0 Z
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楼下等全文~~~8 c# Z3 H  A; h% P
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DNA Methylation of the Gonadal Aromatase (cyp19a) Promoter Is Involved in Temperature-Dependent Sex Ratio Shifts in the European Sea Bass.
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Navarro-Martín L, Viñas J, Ribas L, Díaz N, Gutiérrez A, et al.
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# w/ X% m/ y  O! @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.
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( c, ^. B6 j: w; n! }0 _- k 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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