Reversible DNA methylation regulates seasonal photoperiodic time measurement
Reversible DNA methylation regulates seasonal photoperiodic time measurement
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DOI：
10.1073/pnas.1310643110
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发表时间：
2013-10-08
影响因子：
11.1
通讯作者：
Prendergast, Brian J.
中科院分区：
文献类型：
--
作者：
Stevenson, Tyler J.;Prendergast, Brian J.
在季节性繁殖的脊椎动物中，白天长度的变化通过甲状腺激素依赖机制诱导明显不同的行为和生殖表型。冬季光周期抑制生殖神经内分泌功能，但不能维持这种抑制超过6个月，确保春季生殖复发。这种基因组可塑性表明表观遗传学在建立季节性生殖表型中的作用。在这里，我们报告，DNA甲基化的近端启动子的III型脱碘酶（dio3）基因在仓鼠下丘脑是可逆的，光周期时间测量的关键。短光周期和冬季样褪黑激素抑制下丘脑DNA甲基转移酶的表达，降低dio 3启动子DNA甲基化，上调dio 3的表达，诱导性腺退化。超甲基化减弱了短光周期的生殖反应。春季耐火短光周期重建夏季样甲基化的dio 3启动子，dio 3的表达，和生殖能力，揭示了一个动态和可逆的机制，在哺乳动物大脑中的DNA甲基化，在生理方向的时间起着核心作用。
In seasonally breeding vertebrates, changes in day length induce categorically distinct behavioral and reproductive phenotypes via thyroid hormone-dependent mechanisms. Winter photoperiods inhibit reproductive neuroendocrine function but cannot sustain this inhibition beyond 6 mo, ensuring vernal reproductive recrudescence. This genomic plasticity suggests a role for epigenetics in the establishment of seasonal reproductive phenotypes. Here, we report that DNA methylation of the proximal promoter for the type III deiodinase (dio3) gene in the hamster hypothalamus is reversible and critical for photoperiodic time measurement. Short photoperiods and winter-like melatonin inhibited hypothalamic DNA methyltransferase expression and reduced dio3 promoter DNA methylation, which up-regulated dio3 expression and induced gonadal regression. Hypermethylation attenuated reproductive responses to short photoperiods. Vernal refractoriness to short photoperiods reestablished summer-like methylation of the dio3 promoter, dio3 expression, and reproductive competence, revealing a dynamic and reversible mechanism of DNA methylation in the mammalian brain that plays a central role in physiological orientation in time.