Regulation of hippocampal H3 histone methylation by acute and chronic stress
Regulation of hippocampal H3 histone methylation by acute and chronic stress
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DOI：
10.1073/pnas.0911143106
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发表时间：
2009-12-08
影响因子：
11.1
通讯作者：
McEwen, Bruce S.
中科院分区：
文献类型：
--
作者：
Hunter, Richard G.;McCarthy, Katharine J.;McEwen, Bruce S.
海马体结构是一个大脑区域，以其对应激事件和肾上腺类固醇激素的可塑性而闻名。最近的工作表明，包括海马体在内的不同大脑区域的染色质重塑与各种模型中的应激效应有关。我们选择检测应激、应激持续时间、皮质酮注射和氟西汀治疗对海马组蛋白H3甲基化水平的影响，这些标记分别与活跃转录、异染色质形成和转录抑制相关。我们发现，急性应激增加了齿状回(DG)和CA1中H3K9三甲基化(H3K9me3)的水平，而降低了同一区域的H3K9单甲基化(H3K9me1)和H3K27三甲基化(H3K27me3)的水平，而对H3K4三甲基化(H3K4me3)的水平没有影响。7天的束缚应激降低了CA1中H3K4me3和DG和CA1中H3K27me3的水平，而增加了H3K9me3的基础水平。慢性束缚应激(CRS)21天后，DG中H3K4me3水平轻度升高，H3K9me3水平下降。CRS期间应用氟西汀可逆转DG、H3K9me3的下降，但对其他指标无影响。这些结果显示了应激和抗抑郁治疗所产生的海马区染色质重塑的复杂、惊人的快速和区域性的模式，这可能为理解应激和海马区基因表达的相互作用开辟了一条途径，并揭示了可能被慢性应激减弱或降解的潜在染色质应激反应的轮廓。
The hippocampal formation is a brain region noted for its plasticity in response to stressful events and adrenal steroid hormones. Recent work has shown that chromatin remodeling in various brain regions, including the hippocampus, is associated with the effects of stress in a variety of models. We chose to examine the effects of stress, stress duration, corticosterone administration, and fluoxetine treatment on the levels of hippocampal histone H3 methylation at lysines 4, 9, and 27, marks associated, respectively, with active transcription, heterochromatin formation, and transcriptional repression. We found that acute stress increased the levels of H3K9 tri-methylation (H3K9me3) in the dentate gyrus (DG) and CA1, while it reduced levels of H3K9 mono-methylation (H3K9me1) and H3K27 tri-methylation (H3K27me3) in the same regions, and had no effect on levels of H3K4 tri-methylation (H3K4me3). Seven days of restraint stress reduced levels of H3K4me3 in the CA1 and H3K27me3 in the DG and CA1, while increasing basal levels of H3K9me3. Chronic restraint stress (CRS) for 21 days mildly increased levels of H3K4me3 and reduced H3K9me3 levels in the DG. Treatment with fluoxetine during CRS reversed the decrease in DG H3K9me3, but had no effect on the other marks. These results show a complex, surprisingly rapid, and regionally specific pattern of chromatin remodeling within hippocampus produced by stress and anti-depressant treatment that may open an avenue of understanding the interplay of stress and hippocampal gene expression, and reveal the outlines of a potential chromatin stress response that may be diminished or degraded by chronic stress.