组蛋白H3K36甲基化与心血管发育及疾病的关系

Relationship between histone H3K36 methylation and cardiovascular development and diseases

哺乳动物心脏发育受心脏特异基因转录组以空间/时间的方式精确编码调控。表观遗传因素在心肌细胞的基因转录过程中发挥重要的调控作用。在这些因素中,组蛋白甲基化是真核生物重要的表观遗传修饰之一。其中组蛋白H3第36位赖氨酸(H3K36)的甲基化修饰与基因的转录激活相关,标记了染色质结构中的开放区域。H3K36甲基化的稳态受多种酶和表观因子的协同影响,包括组蛋白甲基转移酶(也称“writer”)、组蛋白去甲基化酶(也称“eraser”)和甲基化组蛋白结合因子(也称“reader”)。H3K36甲基化在神经系统、脂肪组织、心脏及其他器官的发育中起重要作用。H3K36甲基化还参与心脏纤维化、肺动脉高压、心肌肥厚和腹主动脉瘤等多种心血管疾病的发生发展进程。本文综述了组蛋白H3K36甲基化在心血管疾病发生发展中的作用,重点介绍了H3K36甲基转移酶和H3K36去甲基化酶在心血管疾病发生发展中的作用。

Heart development is regulated by the transcriptome of cardiac-specific genes enconded in a spatial/temporal precise manner in mammalians.Epigenetic factors play an critical role in regulating gene transcription in cardiomyocytes.Among these factors,histone methylation is one of the important epigenetic modifications in eukaryotes.Methylation of the 36th lysine of histone H3(H3K36) is associated with the transcriptional activation of genes and marks the open regions of the chromatin.The homeostasis of H3K36methylation is synergistically influenced by various enzymes and regulators,including histone methyltransferases(also called ″writer″),histone demethylases(also called ″eraser″) and methylated histone binding factors(also called ″reader″).H3K36 methylation plays an essential role in the development of the nervous system,adipose tissue,heart and other organs.In recent years,numerous studies have shown that H3K36methylation is also involved in the development of cardiovascular diseases such as cardiac fibrosis,pulmonary hypertension,myocardial hypertrophy and abdominal aortic aneurysm.In this paper,we reviewed the role of histone H3K36 methylation in cardiovascular development and diseases,focusing on the role of H3K36methyltransferases and demethylases in the development of cardiovascular diseases.