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首页> 外文期刊>Frontiers in neuroendocrinology >Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat.
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Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat.

机译：通过DNA甲基化在大鼠中对类固醇受体表达和表型进行母体编程。

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摘要

Increased levels of pup licking/grooming and arched-back nursing by rat mothers over the first week of life alter the epigenome at a glucocorticoid receptor gene promoter in the hippocampus of the offspring. Differences in the DNA methylation pattern between the offspring of High and Low licking/grooming--arched-back mothers emerge over the first week of life, are reversed with cross-fostering, persist into adulthood and are associated with altered histone acetylation and transcription factor (NGFI-A) binding to the glucocorticoid receptor promoter. Central infusion of the adult offspring with the histone deacetylase inhibitor trichostatin A removes the previously defined epigenomic group differences in histone acetylation, DNA methylation, NGFI-A binding, glucocorticoid receptor expression, and hypothalamic-pituitary-adrenal responses to stress, thus suggesting a causal relation between the epigenomic state, glucocorticoid receptor expression and the effects of maternal care on stress responses in theoffspring. These findings demonstrate that an epigenomic state of a gene can be established through a behavioral mode of programming and that in spite of the inherent stability of this epigenomic mark, it is dynamic and potentially reversible.
机译：鼠妈妈在出生后第一周内增加的舔舔/修饰和拱背护理水平改变了后代海马中糖皮质激素受体基因启动子的表观基因组。高和低舔/修饰的后代之间DNA甲基化模式的差异-拱背型母亲在生命的第一周出现，通过交叉培育逆转，持续到成年并与组蛋白乙酰化和转录因子改变有关（NGFI-A）与糖皮质激素受体启动子结合。用组蛋白脱乙酰基酶抑制剂曲古抑菌素A集中输注成年后代，可以消除先前定义的表观基因组差异，包括组蛋白乙酰化，DNA甲基化，NGFI-A结合，糖皮质激素受体表达和下丘脑-垂体-肾上腺对应激的反应，因此表明存在因果关系表基因组状态，糖皮质激素受体表达与母体护理对后代应激反应的影响之间的关系。这些发现表明，可以通过行为的编程模式来建立基因的表观基因组状态，尽管该表观基因组标记具有固有的稳定性，但它是动态的并且可能是可逆的。

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