Perinatal programming of neurodevelopment: epigenetic mechanisms and the prenatal shaping of the brain.
Perinatal programming of neurodevelopment: epigenetic mechanisms and the prenatal shaping of the brain.
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DOI：
10.1007/978-1-4939-1372-5_16
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Desplats, Paula A
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文献类型：
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作者：
Desplats, Paula A
近年来，人们对表观遗传机制的了解呈指数级增长，越来越多的证据表明，DNA甲基化和组蛋白修饰与从胚胎发育到记忆形成和行为的广泛生理过程有关。表观遗传学的一个重要特征是将环境输入转化为生物信号的能力，主要是通过对转录组的调节来响应特定的情景。这一特征产生发育可塑性，并允许同一基因的多种表型表现出来。早年是表观遗传变化的特别敏感时期，因为DNA甲基化和组蛋白标记的活跃变化是发育计划的一部分，并对环境线索做出反应，特别是包括心理社会刺激和母体行为。记忆的形成和储存、成年生活中对压力的反应、行为和神经退行性疾病的表现都可以通过表观遗传修饰在有机体中留下印记，这些修饰有助于在出生前或出生后早期塑造大脑。此外，如果这些表观遗传改变被保存在生殖系中，那么一个世代引起的变化很可能被未来的后代继承。因此，跨代遗传编程代表了环境条件可能影响多代人疾病风险的核心机制。随着新技术的出现和疾病相关甲基组的全基因组图谱的实现，表观遗传标记为生物标记物的发现打开了新的来源。
The recent years have witnessed an exponential growth in the knowledge of epigenetic mechanisms, and piling evidence now links DNA methylation and histone modifications with a wide range of physiological processes from embryonic development to memory formation and behavior. Not surprisingly, deregulation of epigenetic modifications is associated with human diseases as well.An important feature of epigenetics is the ability of transducing environmental input into biological signaling, mainly by modulation of the transcriptome in response to a particular scenario. This characteristic generates developmental plasticity and allows the manifestation of a variety of phenotypes from the same genome.The early-life years represent a period of particular susceptibility to epigenetic alteration, as active changes in DNA methylation and histone marks are occurring as part of developmental programs and in response to environmental cues, which notably include psychosocial stimulation and maternal behavior. Memory formation and storage, response to stress in adult life, behavior, and manifestation of neurodegenerative conditions can all be imprinted in the organism by epigenetic modifications that contribute to shape the brain during prenatal or early postnatal life. Moreover, if these epigenetic alterations are preserved in the germ line, changes induced in one generation are likely inherited by future offspring. Programming by transgenerational inheritance thus represents a central mechanism by which environmental conditions may influence disease risk across multiple generations.As novel techniques emerge and as genome-wide profiling of disease-associated methylomes is achieved, epigenetic marks open a new source for biomarker discovery.