Epigenetic programming by maternal behavior
Epigenetic programming by maternal behavior
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DOI：
10.1038/nn1276
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发表时间：
2004-08-01
影响因子：
25
通讯作者：
Meaney, MJ
中科院分区：
文献类型：
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作者：
Weaver, ICG;Cervoni, N;Meaney, MJ
在这里，我们报告了增加的幼鼠舔和梳理(LG)和拱背哺乳(ABN)的大鼠母亲改变了后代海马糖皮质激素受体(GR)基因启动子的表观基因组。研究发现，与低LG-ABN母亲的后代相比，LG和ABN水平高的母亲的后代在DNA甲基化方面存在差异。这些差异出现在生命的第一周，随着交叉培养而逆转，一直持续到成年，并与组蛋白乙酰化和转录因子(NGFI-A)与GR启动子结合的改变有关。中枢输注组蛋白去乙酰酶抑制剂消除了组蛋白乙酰化、DNA甲基化、NGFI-A结合、GR表达和下丘脑-垂体-肾上腺(HPA)对应激反应的差异，表明表观基因组状态、GR表达和母体对子代应激反应的影响之间存在因果关系。因此，我们表明，一个基因的表观基因组状态可以通过行为编程来建立，并且这种状态是潜在的可逆的。
Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary- adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.