Concordance in hippocampal and fecal Nr3c1 methylation is moderated by maternal behavior in the mouse.

Concordance in hippocampal and fecal Nr3c1 methylation is moderated by maternal behavior in the mouse.
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DOI:
10.1002/ece3.416
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发表时间:
2012-12
影响因子:
2.6
通讯作者:
Champagne, Frances A.
Champagne, Frances A.
中科院分区:
生物学2区
文献类型:
--
作者:
Liberman, Shayna A.;Mashoodh, Rahia;Thompson, Robert C.;Dolinoy, Dana C.;Champagne, Frances A.

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基因组技术的最新进展使分子生物学和进化生物学得以重新结合。因此,研究自然生活动物种群的研究人员越来越能够利用基因组技术将分子发现与生物组织的多个层次联系起来。在实验室中使用这种垂直方法,表观遗传基因调控已成为整合基因型和表型的重要机制。然而,为了将表型与种群适应度联系起来,同样的垂直方法现在必须应用于自然生活的种群。在非侵入性样本中研究表观遗传学的一个主要障碍是表观遗传标记的组织特异性。在这里,使用小鼠作为原理验证模型,我们提出了第一个已知的尝试来验证用于非侵入性样品的表观遗传分析。具体来说,我们比较了接受过不同程度产后母亲护理的Balb/c幼年小鼠中枢(海马)和外周无创(粪便)组织中糖皮质激素受体(Nr3c1)基因启动子中NGFI-A(神经生长因子诱导蛋白A)结合位点的DNA甲基化。我们的研究结果表明,虽然海马DNA甲基化谱与母体行为相对应,但粪便DNA甲基化水平与母体行为无关。此外,个体内部这些组织之间甲基化水平的一致性只有在考虑了产后产妇护理的影响后才会出现。因此,尽管这些发现可能是特异性的Nr3c1基因,但我们敦促在解释非侵入性组织的DNA甲基化模式时要谨慎,并为该领域的进一步研究提供建议。
Recent advances in genomic technologies now enable a reunion of molecular and evolutionary biology. Researchers investigating naturally living animal populations are thus increasingly able to capitalize upon genomic technologies to connect molecular findings with multiple levels of biological organization. Using this vertical approach in the laboratory, epigenetic gene regulation has emerged as an important mechanism integrating genotype and phenotype. To connect phenotype to population fitness, however, this same vertical approach must now be applied to naturally living populations. A major obstacle to studying epigenetics in noninvasive samples is tissue specificity of epigenetic marks. Here, using the mouse as a proof-of-principle model, we present the first known attempt to validate an epigenetic assay for use in noninvasive samples. Specifically, we compare DNA methylation of the NGFI-A (nerve growth factor-inducible protein A) binding site in the promoter of the glucocorticoid receptor (Nr3c1) gene between central (hippocampal) and peripheral noninvasive (fecal) tissues in juvenile Balb/c mice that had received varying levels of postnatal maternal care. Our results indicate that while hippocampal DNA methylation profiles correspond to maternal behavior, fecal DNA methylation levels do not. Moreover, concordance in methylation levels between these tissues within individuals only emerges after accounting for the effects of postnatal maternal care. Thus, although these findings may be specific to the Nr3c1 gene, we urge caution when interpreting DNA methylation patterns from noninvasive tissues, and offer suggestions for further research in this field.
DOI: 10.1002/etc.1707
发表时间: 2012-02-01
影响因子: 4.1
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期刊: EPIGENETICS
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影响因子: 15.1
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