Diet and the epigenetic (re)programming of phenotypic differences in behavior.
Diet and the epigenetic (re)programming of phenotypic differences in behavior.
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DOI：
10.1016/j.brainres.2008.07.074
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发表时间：
2008-10-27
期刊：
影响因子：
2.9
通讯作者：
Szyf M
中科院分区：
文献类型：
--
作者：
McGowan PO;Meaney MJ;Szyf M
表型多样性是由遗传和表观遗传机制形成的，这些机制编程了基因表达的组织特异性模式。包括神经元在内的细胞在发育过程中通过染色质结构的修饰和DNA甲基化的共价修饰进行大规模的表观遗传重编程。有证据表明，这些变化是敏感的环境影响，如母亲的行为和饮食，导致持续的表型差异。例如，影响后代应激反应的大鼠母体行为的自然变化诱导了基因表达的长期变化，包括糖皮质激素受体的变化，这些变化与组蛋白乙酰化、DNA甲基化和NGFI-A转录因子结合的改变有关。这些影响可以通过出生后早期的交叉培养和成年期的药理学操作来逆转，包括曲古抑菌素A（TSA）和L-甲硫氨酸给药，影响大脑中关键位点的表观遗传状态。由于蛋氨酸水平受饮食影响，这些影响表明饮食可能对这种行为可塑性有显着贡献。最近的数据表明，类似的机制可能会影响人类的行为和心理健康。流行病学数据表明，膳食中甲基含量的变化确实会影响DNA甲基化和基因表达编程。怀孕期间的营养限制可能会影响大脑中的表观遗传编程。这些发现提供了一个稳定而动态的表观基因组能够通过表观遗传编程调节表型可塑性的证据。
Phenotypic diversity is shaped by both genetic and epigenetic mechanisms that program tissue specific patterns of gene expression. Cells, including neurons, undergo massive epigenetic reprogramming during development through modifications to chromatin structure, and by covalent modifications of the DNA through methylation. There is evidence that these changes are sensitive to environmental influences such as maternal behavior and diet, leading to sustained differences in phenotype. For example, natural variations in maternal behavior in the rat that influence stress reactivity in offspring induce long-term changes in gene expression, including in the glucocorticoid receptor, that are associated with altered histone acetylation, DNA methylation, and NGFI-A transcription factor binding. These effects can be reversed by early postnatal cross-fostering, and by pharmacological manipulations in adulthood, including Trichostatin A (TSA) and L-methionine administration, that influence the epigenetic status of critical loci in the brain. Because levels of methionine are influenced by diet, these effects suggest that diet could contribute significantly to this behavioral plasticity. Recent data suggest that similar mechanisms could influence human behavior and mental health. Epidemiological data suggest indeed that dietary changes in methyl contents could affect DNA methylation and gene expression programming. Nutritional restriction during gestation could affect epigenetic programming in the brain. These findings provide evidence for a stable yet dynamic epigenome capable of regulating phenotypic plasticity through epigenetic programming.
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