运动对骨骼肌基因表达的表观遗传调控作用

DNA甲基化、组蛋白修饰和miRNA表达调控是表观遗传调控的3种重要方式,其在基因表达调控中发挥着关键作用。适当运动有益于身心健康。骨骼肌作为运动的主体组织,运动可以提高其代谢能力,改善其线粒体生物学功能,调控肌纤维类型转化,增加骨骼肌力量。近年来越来越多的研究表明,表观遗传调控在机体适应运动过程中发挥着重要作用,DNA甲基化、组蛋白修饰和miRNA表达调控等表观遗传调控方式通过调控骨骼肌基因表达来改变骨骼肌代谢能力、线粒体生物学功能和肌纤维类型,从而适应运动变化。本文对近年来运动对骨骼肌基因DNA甲基化、组蛋白修饰和相应miRNA表达调控等3种表观遗传调控方式的研究现状进行了综述,以期为进一步研究运动改善机体机能和健康提供参考。     

表观遗传修饰介导的植物胁迫记忆

植物因其固着生长的方式, 已经进化出各类特殊的机制来适应多变的外界环境。为提高自身的存活率, 植物进化出一类胁迫记忆机制, 以适应环境和保护自己。表观遗传修饰不仅能调控植物的正常生长发育, 而且参与植物对各种非生物或生物胁迫的响应。近年的研究表明, 表观遗传修饰在植物胁迫记忆调控中也发挥重要作用。例如, DNA甲基化、组蛋白甲基化及乙酰化等表观遗传修饰参与并维持特定的胁迫记忆。该文主要对表观遗传修饰介导的植物胁迫记忆最新进展进行综述, 并展望未来的重点和热点研究方向。     

表观遗传修饰介导的植物胁迫记忆

植物因其固着生长的方式, 已经进化出各类特殊的机制来适应多变的外界环境。为提高自身的存活率, 植物进化出一类胁迫记忆机制, 以适应环境和保护自己。表观遗传修饰不仅能调控植物的正常生长发育, 而且参与植物对各种非生物或生物胁迫的响应。近年的研究表明, 表观遗传修饰在植物胁迫记忆调控中也发挥重要作用。例如, DNA甲基化、组蛋白甲基化及乙酰化等表观遗传修饰参与并维持特定的胁迫记忆。该文主要对表观遗传修饰介导的植物胁迫记忆最新进展进行综述, 并展望未来的重点和热点研究方向。     

哺乳动物细胞衰老调节的新机制——端粒的表观遗传修饰

端粒（telomere）是位于真核生物染色体末端的保护性结构,在调节细胞衰老及细胞寿命等 方面具有重要意义.人们已在端粒结构中鉴定出了一系列的蛋白因子,如TRF1、TRF2、Pot1 ,Rap1、Tin2等,这些因子在保护端粒以及维持端粒合适长度的过程中具有重要作用.最近 人们发现,在端粒结构以及亚端粒区域中存在丰富的表观遗传修饰,该类修饰包括组蛋白的 三甲基化、组蛋白的乙酰基化以及DNA的甲基化等.并且发现这些修饰在端粒长度调节过程以 及端粒相关疾病的发生发展过程中具有重要意义.人们推测,该机制可能对哺乳动物的衰老过 程以及衰老相关的疾病等方面具有重要的调节作用.本文将对这些方面的最新研究进展作一 介绍.     

组蛋白甲基化修饰效应分子的研究进展

作为一种重要的表观遗传学调控机制,组蛋白甲基化修饰在多种生命过程中发挥了重要的作用。细胞内有多种组蛋白甲基化酶和去甲基化酶共同调节组蛋白的修饰状态,在组蛋白甲基化状态确定后,多种效应分子特异的读取修饰信息,从而参与基因转录调控过程。文章从组蛋白甲基化效应分子的作用机制方面综述了这一领域的研究进展。     

表观遗传与microRNA相互调控机制以及在抗肿瘤领域内的应用

DNA甲基化和组蛋白修饰等表观遗传机制是恶性肿瘤发生发展的重要原因之一．然而近年来研究发现,microRNA表达水平改变也参与恶性肿瘤的形成．最新研究资料揭示,表观遗传可调控microRNA表达,而一些种类的microRNA也可调节表观遗传,并且二者之间相互作用可调控组织细胞内基因表达以及诱导体内恶性肿瘤产生．研究资料还显示,表观遗传主要通过DNA甲基化、组蛋白修饰等方式调控microRNA表达,而microRNA则通过调节DNA甲基化转移酶、维持细胞中DNA甲基化水平或改变组蛋白修饰等途径调控表观遗传．对microRNA与表观遗传之间的调控关系以及在抗肿瘤领域内的应用进行全面而系统的论述．     

表观遗传学与子宫内膜癌的研究进展

长期以来人们一直认为基因突变或缺失参与肿瘤的形成,近年来越来越多证据表明,表观遗传修饰在肿瘤进展中同样具有非常重要的作用。DNA甲基化、组蛋白修饰及microRNA表达调控等表观遗传机制是子宫内膜癌发生、发展的重要原因之一。表观遗传学的研究进展不仅有助于子宫内膜癌的早期诊断,对分子靶向治疗子宫内膜癌亦显示出良好的应用前景。     

表观遗传学与子宫内膜癌的研究进展

长期以来人们一直认为基因突变或缺失参与肿瘤的形成,近年来越来越多证据表明,表观遗传修饰在肿瘤进展中同样具有非常重要的作用。DNA甲基化、组蛋白修饰及micro RNA表达调控等表观遗传机制是子宫内膜癌发生、发展的重要原因之一。表观遗传学的研究进展不仅有助于子宫内膜癌的早期诊断,对分子靶向治疗子宫内膜癌亦显示出良好的应用前景。     

表观遗传调控植物逆境胁迫的适应机制

植物表观遗传学不仅是基础科学研究的焦点,也是植物育种中获得新资源的一种方式。表观遗传机制可以通过非编码RNA,组蛋白修饰和DNA甲基化控制基因的表达,且越来越多的研究表明表观遗传机制对植物适应环境及胁迫记忆是必要的。本综述重点从DNA甲基化调控、组蛋白变异、组蛋白修饰调控、非编码RNA调控水平论述植物在各种逆境条件下如何通过表观遗传机制来适应环境。     

组蛋白去甲基化酶与肿瘤发生

组蛋白甲基化修饰是一个可逆的动态的调节过程。甲基化和/或去甲基化状态与表观遗传、转录调控和维持基因组完整性等密切相关。组蛋白甲基化状态异常会直接或间接影响各种生理和病理过程。已知组蛋白去甲基化酶包括赖氨酸特异性去甲基化酶（LSD）家族和含JmjC结构域的JMJD家族。研究发现,两者与肿瘤的发生均有着密切的关系。本文总结了组蛋白去甲基化酶在组蛋白甲基化修饰及肿瘤研究方面的最新进展,为组蛋白修饰的功能及肿瘤诊断、治疗、预后监测等研究提供新思路。在胃癌、乳腺癌、结肠癌等常见肿瘤中,组蛋白去甲基化酶可改变组蛋白的甲基化水平或者直接作用于癌基因,也可调节microRNA或转录因子等,促进或抑制肿瘤的发生发展与影响肿瘤的预后。     

杂种优势形成的表观遗传学研究进展

杂种优势是一种复杂的生物学现象,在农业生产上得到了广泛的应用,但对其形成的遗传机理和分子基础尚不清楚。随着表观遗传学的深入研究,尤其是DNA甲基化、小分子RNA和组蛋白修饰等技术的发展,为杂种优势形成的分子基础提供了新的研究策略和技术手段。DNA甲基化、小分子RNA、组蛋白三者在杂交种中水平的改变与杂种优势有着一定关系,同时,三者之间相互作用调节基因表达影响杂种优势。本文简述了近年来表观遗传学在杂种优势形成中的作用和遗传机制等方面的研究进展,并且提出了目前存在的问题和下一步的研究方向。本综述将有助于从表观遗传学的角度认识杂种优势的形成机理,从而促进对杂种优势的表观遗传学基础的理解及其在植物杂交育种上的应用研究。     

Histone methylation makes its mark on longevity

How long organisms live is not entirely written in their genes. Recent findings reveal that epigenetic factors that regulate histone methylation, a type of chromatin modification, can affect lifespan. The reversible nature of chromatin modifications suggests that therapeutic targeting of chromatin regulators could be used to extend lifespan and healthspan. This review describes the epigenetic regulation of lifespan in diverse model organisms, focusing on the role and mode of action of chromatin regulators that affect two epigenetic marks, trimethylated lysine 4 of histone H3 (H3K4me3) and trimethylated lysine 27 of histone H3 (H3K27me3), in longevity.     

Silencing of transgene expression in mammalian cells by DNA methylation and histone modifications in gene therapy perspective

DNA methylation and histone modifications are vital in maintaining genomic stability and modulating cellular functions in mammalian cells. These two epigenetic modifications are the most common gene regulatory systems known to spatially control gene expression. Transgene silencing by these two mechanisms is a major challenge to achieving effective gene therapy for many genetic conditions. The implications of transgene silencing caused by epigenetic modifications have been extensively studied and reported in numerous gene delivery studies. This review highlights instances of transgene silencing by DNA methylation and histone modification with specific focus on the role of these two epigenetic effects on the repression of transgene expression in mammalian cells from integrative and non-integrative based gene delivery systems in the context of gene therapy. It also discusses the prospects of achieving an effective and sustained transgene expression for future gene therapy applications.     

Histone methylation: a dynamic mark in health, disease and inheritance

Organisms require an appropriate balance of stability and reversibility in gene expression programmes to maintain cell identity or to enable responses to stimuli; epigenetic regulation is integral to this dynamic control. Post-translational modification of histones by methylation is an important and widespread type of chromatin modification that is known to influence biological processes in the context of development and cellular responses. To evaluate how histone methylation contributes to stable or reversible control, we provide a broad overview of how histone methylation is regulated and leads to biological outcomes. The importance of appropriately maintaining or reprogramming histone methylation is illustrated by its links to disease and ageing and possibly to transmission of traits across generations.     

Epigenetic regulation by histone methylation and histone variants

Epigenetics is the study of heritable changes in gene expression that are not mediated at the DNA sequence level. Molecular mechanisms that mediate epigenetic regulation include DNA methylation and chromatin/histone modifications. With the identification of key histone-modifying enzymes, the biological functions of many histone posttranslational modifications are now beginning to be elucidated. Histone methylation, in particular, plays critical roles in many epigenetic phenomena. In this review, we provide an overview of recent findings that shape the current paradigms regarding the roles of histone methylation and histone variants in heterochromatin assembly and the maintenance of the boundaries between heterochromatin and euchromatin. We also highlight some of the enzymes that mediate histone methylation and discuss the stability and inheritance of this modification.     

Structural biology-based insights into combinatorial readout and crosstalk among epigenetic marks

Epigenetic mechanisms control gene regulation by writing, reading and erasing specific epigenetic marks. Within the context of multi-disciplinary approaches applied to investigate epigenetic regulation in diverse systems, structural biology techniques have provided insights at the molecular level of key interactions between upstream regulators and downstream effectors. The early structural efforts focused on studies at the single domain-single mark level have been rapidly extended to research at the multiple domain–multiple mark level, thereby providing additional insights into connections within the complicated epigenetic regulatory network. This review focuses on recent results from structural studies on combinatorial readout and crosstalk among epigenetic marks. It starts with an overview of multiple readout of histone marks associated with both single and dual histone tails, as well as the potential crosstalk between them. Next, this review further expands on the simultaneous readout by epigenetic modules of histone and DNA marks, thereby establishing connections between histone lysine methylation and DNA methylation at the nucleosomal level. Finally, the review discusses the role of pre-existing epigenetic marks in directing the writing/erasing of certain epigenetic marks. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function.