Circadian behavior is light-reprogrammed by plastic DNA methylation
Circadian behavior is light-reprogrammed by plastic DNA methylation
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DOI：
10.1038/nn.3651
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发表时间：
2014-03-01
影响因子：
25
通讯作者：
Brown, Steven A.
中科院分区：
文献类型：
--
作者：
Azzi, Abdelhalim;Dallmann, Robert;Brown, Steven A.
不同个体之间的日常昼夜节律行为时间可能存在很大差异，双胞胎研究表明，这种变化大约有一半是环境控制的。在暴露于改变的照明环境（例如 22 小时而不是 24 小时）的小鼠中也可以看到类似的可塑性，这会稳定地改变基因决定的昼夜节律行为周期数月。调节这些环境影响的机制尚不清楚。我们发现，小鼠短暂暴露在这种照明下会稳定地改变下丘脑视交叉上核（SCN）（调节哺乳动物昼夜节律行为的主时钟组织）的整体转录。与此同时，全基因组甲基化分析揭示了 SCN 中启动子 DNA 甲基化的整体变化，而这些变化与这些变化相关。长时间重新夹带至 24 小时后，行为、转录和 DNA 甲基化变化是可逆的。值得注意的是，向 SCN 输注甲基转移酶抑制剂可抑制周期变化。我们得出的结论是，SCN 利用 DNA 甲基化作为驱动生物钟可塑性的机制。
The timing of daily circadian behavior can be highly variable among different individuals, and twin studies have suggested that about half of this variability is environmentally controlled. Similar plasticity can be seen in mice exposed to an altered lighting environment, for example, 22-h instead of 24-h, which stably alters the genetically determined period of circadian behavior for months. The mechanisms mediating these environmental influences are unknown. We found that transient exposure of mice to such lighting stably altered global transcription in the suprachiasmatic nucleus (SCN) of the hypothalamus (the master clock tissue regulating circadian behavior in mammals). In parallel, genome-wide methylation profiling revealed global alterations in promoter DNA methylation in the SCN that correlated with these changes. Behavioral, transcriptional and DNA methylation changes were reversible after prolonged re-entrainment to 24-h d. Notably, infusion of a methyltransferase inhibitor to the SCN suppressed period changes. We conclude that the SCN utilizes DNA methylation as a mechanism to drive circadian clock plasticity.