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新挑战:线粒体表观遗传学?

New Challenge: Mitochondrial Epigenetics?

机构信息

Reproductive Unit, Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, 1000, Ljubljana, Slovenia.

出版信息

Stem Cell Rev Rep. 2018 Feb;14(1):13-26. doi: 10.1007/s12015-017-9771-z.

Abstract

Epigenetics can be explored at different levels and can be divided into two major areas: epigenetics of nuclear-encoded DNA and epigenetics of mitochondrial-encoded DNA. In epigenetics of nuclear-encoded DNA, the main roles are played by DNA methylation, changes in histone structure and several types of non-coding RNAs. Mitochondrial epigenetics seems to be similar in the aspect of DNA methylation and to some extent in the role of non-coding RNAs but differs significantly in changes in components coiling DNA. Nuclear DNA is coiled around histones, but mitochondrial DNA, together with associated proteins, is located in mitochondrial pseudocompartments called nucleoids. It has been shown that mitochondrial epigenetic mechanisms influence cell fate, transcription regulation, cell division, cell cycle, physiological homeostasis, bioenergetics and even pathologies, but not all of these mechanisms have been explored in stem cells. The main issue is that most of these mechanisms have only recently been discovered in mitochondria, while improvements in methodology, especially next-generation sequencing, have enabled in-depth studies. Because studies exploring mitochondria from other aspects show that mitochondria are crucial for the normal behavior of stem cells, it is suggested that precise mitochondrial epigenetics in stem cells should be studied more intensively.

摘要

表观遗传学可以在不同层面进行探索,可分为两大主要领域:核编码 DNA 的表观遗传学和线粒体编码 DNA 的表观遗传学。在核编码 DNA 的表观遗传学中,主要作用是 DNA 甲基化、组蛋白结构的变化和几种类型的非编码 RNA。线粒体表观遗传学在 DNA 甲基化方面似乎相似,在非编码 RNA 的作用方面在某种程度上也相似,但在线粒体 DNA 成分卷曲方面存在显著差异。核 DNA 缠绕在组蛋白周围,但线粒体 DNA 与相关蛋白一起位于称为类核的线粒体拟核区。已经表明,线粒体表观遗传机制影响细胞命运、转录调控、细胞分裂、细胞周期、生理稳态、生物能量学甚至病理学,但并非所有这些机制都在干细胞中得到了探索。主要问题是,这些机制中的大多数最近才在线粒体中被发现,而方法学的改进,特别是下一代测序技术,使得深入研究成为可能。由于从其他方面探索线粒体的研究表明线粒体对于干细胞的正常行为至关重要,因此建议更深入地研究干细胞中的精确线粒体表观遗传学。

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