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。     

Does skeletal muscle have an ‘epi’‐memory? The role of epigenetics in nutritional programming,metabolic disease,aging and exercise

Skeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can ‘remember’ early‐life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an ‘epi’‐memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re‐encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early‐life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise‐induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the ‘epi’‐memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging.     

Genome‐wide DNA methylation changes with age in disease‐free human skeletal muscle

A decline in skeletal muscle mass and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report for the first time a genome‐wide study of DNA methylation dynamics in skeletal muscle of healthy male individuals during normal human aging. We predominantly observed hypermethylation throughout the genome within the aged group as compared to the young subjects. Differentially methylated CpG (dmCpG) nucleotides tend to arise intragenically and are underrepresented in promoters and are overrepresented in the middle and 3′ end of genes. The intragenic methylation changes are overrepresented in genes that guide the formation of the junction of the motor neuron and myofibers. We report a low level of correlation of gene expression from previous studies of aged muscle with our current analysis of DNA methylation status. For those genes that had both changes in methylation and gene expression with age, we observed a reverse correlation, with the exception of intragenic hypermethylated genes that were correlated with an increased gene expression. We suggest that a minimal number of dmCpG sites or select sites are required to be altered in order to correlate with gene expression changes. Finally, we identified 500 dmCpG sites that perform well in discriminating young from old samples. Our findings highlight epigenetic links between aging postmitotic skeletal muscle and DNA methylation.     

LncRNA调控骨骼肌发育的分子机制及其在家养动物中的研究进展

骨骼肌是维持机体功能必不可少的组织,与家养动物的产肉率等重要经济性状密切相关。近年来,高通量测序鉴定了大量与骨骼肌生成相关的长链非编码RNA (long non-coding RNA, lncRNA),它们可作为调节因子在表观调控、转录调控以及转录后调控等多个层面调控基因表达。lncRNA通过靶向关键因子参与调控骨骼肌发育的各个环节,包括骨骼肌干细胞增殖、迁移、分化,成肌细胞增殖、分化、肌管融合,肌纤维肥大和纤维类型转换等过程。本文重点归纳了lncRNA在人和小鼠骨骼肌发育中的分子调控机制,介绍了lncRNA的研究方法,综述了lncRNA在家养动物骨骼肌发育中的研究进展,分析了目前家养动物lncRNA研究所面临的困难和挑战,最后展望了未来家养动物lncRNA研究的方向,以期为进一步阐明骨骼肌生长发育的分子调控机制提供参考。     

Mechanisms of epigenetic memory and addiction

Epigenetic regulation of cellular identity and function is at least partly achieved through changes in covalent modifications on DNA and histones. Much progress has been made in recent years to understand how these covalent modifications affect cell identity and function. Despite the advances, whether and how epigenetic factors contribute to memory formation is still poorly understood. In this review, we discuss recent progress in elucidating epigenetic mechanisms of learning and memory, primarily at the DNA level, and look ahead to discuss their potential implications in reward memory and development of drug addiction.     

调控肌肉生长发育的lncRNAs

长链非编码RNA（long non-coding RNA, lncRNA）是存在于真核生物体内的一种长度大于200 nt主要由RNA聚合酶Ⅱ转录而来的RNAs,且不具有编码蛋白质能力。作为机体基因调控网络的重要调节因子,lncRNA在X染色体沉默、脂肪代谢、细胞生长发育等方面发挥重要作用。近期研究结果表明,lncRNA通过介导表观遗传、转录水平和转录后水平调控等方式,参与骨骼肌的生长发育以及分化过程的调节,包括调控肌源性干细胞和成肌细胞的增殖、分化和肌管的融合等进程,从而影响肌肉的生长发育。本文概述了lncRNA的分类与生物学功能,归纳了lncRNA的作用机制,重点介绍参与骨骼肌生长发育调控的lncRNAs,分析目前lncRNA研究面临的机遇及挑战,展望未来研究的热点与方向,以期为lncRNA在肌肉生长调控方面开展深入研究提供参考。     

Mitotic inheritance of DNA methylation: more than just copy and paste

Decades of investigation on DNA methylation have led to deeper insights into its metabolic mechanisms and biological functions.This understanding was fueled by the recent development of genome editing tools and our improved capacity for analyzing the global DNA methylome in mammalian cells.This review focuses on the maintenance of DNA methylation patterns during mitotic cell division.We discuss the latest discoveries of the mechanisms for the inheritance of DNA methylation as a stable epigenetic memory.We also highlight recent evidence showing the rapid turnover of DNA methylation as a dynamic gene regulatory mechanism.A body of work has shown that altered DNA methylomes are common features in aging and disease.We discuss the potential links between methylation maintenance mechanisms and diseaseassociated methylation changes.