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生殖系永生的表观遗传学:来自优雅模型系统的启示。

The epigenetics of germ-line immortality: lessons from an elegant model system.

机构信息

Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

出版信息

Dev Growth Differ. 2010 Aug;52(6):527-32. doi: 10.1111/j.1440-169X.2010.01179.x.

Abstract

Epigenetic mechanisms are thought to help regulate the unique transcription program that is established in germ cell development. During the germline cycle of many organisms, the epigenome undergoes waves of extensive resetting events, while a part of epigenetic modification remains faithful to specific loci. Little is known about the mechanisms underlying these events, how loci are selected for, or avoid, reprogramming, or even why these events are required. In particular, although the significance of genomic imprinting phenomena involving DNA methylation in mammals is now well accepted, the role of histone modification as a transgenerational epigenetic mechanism has been the subject of debate. Such epigenetic mechanisms may help regulate transcription programs and/or the pluripotent status conferred on germ cells, and contribute to germ line continuity across generations. Recent studies provide new evidence for heritability of histone modifications through germ line cells and its potential effects on transcription regulation both in the soma and germ line of subsequent generations. Unraveling transgenerational epigenetic mechanisms involving highly conserved histone modifications in elegant model systems will accelerate the generation of new paradigms and inspire research in a wide variety of fields, including basic developmental studies and clinical stem cell research.

摘要

表观遗传机制被认为有助于调节生殖细胞发育中建立的独特转录程序。在许多生物体的生殖系周期中,表观基因组经历了广泛的重置事件波,而一部分表观遗传修饰仍然忠实于特定的基因座。对于这些事件的发生机制、基因座如何被选择进行或避免重编程,甚至为什么需要这些事件,我们知之甚少。特别是,尽管涉及哺乳动物 DNA 甲基化的基因组印迹现象的意义现在已被广泛接受,但组蛋白修饰作为一种跨代表观遗传机制的作用一直是争论的主题。这种表观遗传机制可能有助于调节转录程序和/或赋予生殖细胞的多能状态,并有助于跨代生殖系的连续性。最近的研究为通过生殖系细胞遗传组蛋白修饰及其对随后几代体细胞核生殖系中转录调控的潜在影响提供了新的证据。在优雅的模式系统中揭示涉及高度保守的组蛋白修饰的跨代表观遗传机制将加速新范式的产生,并激发包括基础发育研究和临床干细胞研究在内的广泛领域的研究。

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