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心脏中的表观遗传学:组蛋白修饰在心脏重构中的作用。

Epigenetics in the heart: the role of histone modifications in cardiac remodelling.

机构信息

Babraham Institute, Babraham, Cambridge CB22 3AT, England, UK.

出版信息

Biochem Soc Trans. 2013 Jun;41(3):789-96. doi: 10.1042/BST20130012.

Abstract

Understanding the molecular mechanisms underlying cardiac development and growth has been a longstanding goal for developing therapies for cardiovascular disorders. The heart adapts to a rise in its required output by an increase in muscle mass and alteration in the expression of a large number of genes. However, persistent stress diminishes the plasticity of the heart, consequently resulting in its maladaptive growth, termed pathological hypertrophy. Recent developments suggest that the concomitant genome-wide remodelling of the gene expression programme is largely driven through epigenetic mechanisms such as post-translational histone modifications and DNA methylation. In the last few years, the distinct functions of histone modifications and of the enzymes catalysing their formation have begun to be elucidated in processes important for cardiac development, disease and cardiomyocyte proliferation. The present review explores how repressive histone modifications, in particular methylation of H3K9 (histone H3 Lys9), govern aspects of cardiac biology.

摘要

了解心脏发育和生长的分子机制一直是开发心血管疾病治疗方法的长期目标。心脏通过增加肌肉质量和改变大量基因的表达来适应其所需输出的增加。然而,持续的压力会降低心脏的可塑性,从而导致其适应性生长,即病理性肥大。最近的研究表明,基因表达程序的全基因组重塑在很大程度上是通过表观遗传机制驱动的,如翻译后组蛋白修饰和 DNA 甲基化。在过去的几年中,组蛋白修饰的不同功能及其形成的酶的催化作用在心脏发育、疾病和心肌细胞增殖的重要过程中开始被阐明。本综述探讨了抑制性组蛋白修饰,特别是 H3K9(组蛋白 H3 赖氨酸 9)的甲基化,如何控制心脏生物学的各个方面。

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