The physics of epigenetics
The physics of epigenetics
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DOI：
10.1103/revmodphys.88.025002
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发表时间：
2016-04-26
影响因子：
44.1
通讯作者：
Victor, Jean-Marc
中科院分区：
文献类型：
--
作者：
Cortini, Ruggero;Barbi, Maria;Victor, Jean-Marc
在高等生物中，所有细胞都有相同的基因组，但每个细胞只表达一组有限的特定基因，这些基因定义了细胞类型。在细胞分裂过程中，不仅基因组，而且细胞类型也由子细胞继承。这种有趣的现象是通过各种过程实现的，这些过程被统称为表观遗传学：基因表达模式中稳定的和可遗传的变化。本文回顾了控制表观遗传状态启动、传播和遗传背后的生物过程的极其丰富且精致的多尺度物理机制。这些变化不仅包括与DNA和组蛋白的化学修饰（如甲基化和乙酰化）相关的分子性质的变化，还包括不太常见的变化，通常是在控制细胞核中基因组三维组织的物理学中。引人注目的是，为了实现表观遗传状态的稳定性和遗传性，细胞利用了许多不同的物理原理，例如聚合物和共聚物的普遍行为，动力学系统的一般特征，以及与DNA和组蛋白的化学修饰相关的静电和机械性质。将复杂的生物学文献置于新的视角下，新出现的图景是，一套有限的一般物理规则在启动、塑造和传递这一关键的“表观遗传景观”中发挥了关键作用。“这种新的视角不仅使人们能够合理化正常的细胞功能，而且还有助于理解病理状态的出现，其中表观遗传景观变得功能失调。
In higher organisms, all cells share the same genome, but every cell expresses only a limited and specific set of genes that defines the cell type. During cell division, not only the genome, but also the cell type is inherited by the daughter cells. This intriguing phenomenon is achieved by a variety of processes that have been collectively termed epigenetics: the stable and inheritable changes in gene expression patterns. This article reviews the extremely rich and exquisitely multiscale physical mechanisms that govern the biological processes behind the initiation, spreading, and inheritance of epigenetic states. These include not only the changes in the molecular properties associated with the chemical modifications of DNA and histone proteins, such as methylation and acetylation, but also less conventional changes, typically in the physics that governs the three-dimensional organization of the genome in cell nuclei. Strikingly, to achieve stability and heritability of epigenetic states, cells take advantage of many different physical principles, such as the universal behavior of polymers and copolymers, the general features of dynamical systems, and the electrostatic and mechanical properties related to chemical modifications of DNA and histones. By putting the complex biological literature in this new light, the emerging picture is that a limited set of general physical rules play a key role in initiating, shaping, and transmitting this crucial "epigenetic landscape." This new perspective not only allows one to rationalize the normal cellular functions, but also helps to understand the emergence of pathological states, in which the epigenetic landscape becomes dysfunctional.