Epigenetics: unforeseen regulators in cancer

The past several years have seen a tremendous advance in the understanding of the basic mechanisms of epigenetic regulation. A large number of studies have not only linked epigenetics with cell cycle regulation but also partially unravelled how epigenetics may regulate gene expression. The aim of this review is to provide an overview of the latest findings and current ideas on epigenetics with a focus on emphasizing the emerging influence epigenetics has on the onset and progression of cancer.     

植物组蛋白去乙酰化酶的特性及功能

真核生物染色质修饰是基因表达调控中的一个重要部分,组蛋白乙酰化修饰是基因转录调控的关键机制,与基因表达的活跃与沉默密切相关。组蛋白乙酰化修饰已成为表观遗传学的重要组成部分,受到研究者的普遍重视。本文从植物组蛋白去乙酰化酶(histone deacetylase,HDACs)的分类开始,综述植物中HDACs家族成员的结构特点、组织表达的多样性与复杂性,重点阐述其对发育的调控、逆境胁迫的响应。对了解基因的调控机制,丰富表观遗传学内容,并最终应用于植物育种及农业生产具有重要意义。     

昆虫滞育表观遗传调控的研究进展

滞育是昆虫躲避不良环境的一种策略,对延续昆虫种群具有重要意义.特别是昆虫的兼性滞育,能够受环境的周期性季节变化影响,表观遗传可能在其中扮演重要角色.表观遗传是不依赖DNA序列改变所产生的可遗传变异,包括DNA、RNA、蛋白质和染色质水平上的各种表观遗传调控过程,可能参与生物的发育可塑性.昆虫滞育表观遗传调控主要包括两个...     

酵母模式生物研究表观遗传调控基因组稳定性的进展

基因组的遗传稳定性是维持正常的细胞复制、增殖和分化的关键。外源因素和内源因素造成的DNA损伤及其修复失败, 是各种遗传疾病发生的根本原因。表观遗传调控(包括DNA甲基化、组蛋白修饰和非编码RNA)在DNA损伤修复和细胞周期调控方面发挥着重要的作用, 也是维持基因组稳定性的基础。酵母作为单细胞真核生物, 是最早开展表观遗传学研究的物种之一, 特别是在DNA损伤修复和异染色质形成等方面的研究, 为揭示遗传稳定性的本质提供了理论依据。国际上前期以酵母为模式生物研究表观遗传学的报道主要集中于组蛋白修饰领域; 近期利用裂殖酵母作为模式生物研究RNAi指导的组蛋白修饰也有了一定的进展。文章以酵母作为模式生物, 论述了表观遗传修饰在维持基因组遗传稳定性中的研究进展、作用机制和今后的发展趋势。     

Epigenetics, miRNAs, and human cancer: a new chapter in human gene regulation

Cancer is a genetic and epigenetic disease. MicroRNAs (miRNAs), a class of small noncoding RNAs, have been shown to be deregulated in many diseases including cancer. An intertwined connection between epigenetics and miRNAs has been supported by the recent identification of a specific subgroup of miRNAs called “epi-miRNAs” that can directly and indirectly modulate the activity of the epigenetic machinery. The complexity of this connection is enhanced by the epigenetic regulation of miRNA expression that generates a fine regulatory feedback loop. This review focuses on how epigenetics affects the miRNome and how the recently identified epi-miRNAs regulate the epigenome in human cancers, ultimately contributing to human carcinogenesis.     

Epigenetics and cell cycle regulation in cystogenesis

The role of genetic mutations in the development of polycystic kidney disease (PKD), such as alterations in PKD1 and PKD2 genes in autosomal dominant PKD (ADPKD), is well understood. However, the significance of epigenetic mechanisms in the progression of PKD remains unclear and is increasingly being investigated. The term of epigenetics describes a range of mechanisms in genome function that do not solely result from the DNA sequence itself. Epigenetic information can be inherited during mammalian cell division to sustain phenotype specifically and physiologically responsive gene expression in the progeny cells. A multitude of functional studies of epigenetic modifiers and systematic genome-wide mapping of epigenetic marks reveal the importance of epigenomic mechanisms, including DNA methylation, histone/chromatin modifications and non-coding RNAs, in PKD pathologies. Deregulated proliferation is a characteristic feature of cystic renal epithelial cells. Moreover, defects in many of the molecules that regulate the cell cycle have been implicated in cyst formation and progression. Recent evidence suggests that alterations of DNA methylation and histone modifications on specific genes and the whole genome involved in cell cycle regulation and contribute to the pathogenesis of PKD. This review summarizes the recent advances of epigenetic mechanisms in PKD, which helps us to define the term of “PKD epigenetics” and group PKD epigenetic changes in three categories. In particularly, this review focuses on the interplay of epigenetic mechanisms with cell cycle regulation during normal cell cycle progression and cystic cell proliferation, and discusses the potential to detect and quantify DNA methylation from body fluids as diagnostic/prognostic biomarkers. Collectively, this review provides concepts and examples of epigenetics in cell cycle regulation to reveal a broad view of different aspects of epigenetics in biology and PKD, which may facilitate to identify possible novel therapeutic intervention points and to explore epigenetic biomarkers in PKD.     

How to localize epigenetics in the landscape of biological research?

Today, epigenetics is a very fashionable field of research. Modification of DNA by methylation, and of chromatin by histone modification or substitution represents a major fraction of the studies; but this special issue shows that epigenetic studies are very diverse, and not limited to the study of chromatin. What is common behind these different uses of the word epigenetics? A brief historical survey shows that epigenetics was invented twice, with different meanings: in the 1940s, by Conrad Waddington, as the study of the relations between the genotype and the phenotype; in the 1960s, as the global mechanisms of gene regulation involved in differentiation and development; what is common is that an approach distinct from genetics was in both cases considered as necessary because genetic models were incapable to address these problems. A good way to appreciate the relations between genetics and epigenetics is to realize that the main aim of organisms is to reproduce, and to consider the way organisms perform this task. Genetics is the precise means organisms have invented to reproduce the structure of their macromolecular components; the genome is also used to control the level and place of this reproduction. All the other means organisms have used to reproduce were more or less the result of tinkering, and constitute the field of epigenetics, with its diversity and richness.     

Chromatin and epigenetics in development: blending cellular memory with cell fate plasticity

The epigenetic regulation of chromatin structure and composition has often been studied molecularly in the context of specific DNA-dependent processes. However, epigenetics also play important global roles in shaping and maintaining cell identity, and in patterning the body plan during normal development. Moreover, alterations in epigenetic regulation are involved in many diseases, including cancer. The advances in our understanding of the impact of epigenetics in development and disease were discussed at a recent Keystone symposium.     

表观遗传对炎症的调控机制及其在奶牛乳房炎抗病育种中的应用前景

炎症受遗传和非遗传因素(环境或表观遗传)的共同影响, 其中表观遗传(Epigenetic)在炎症的发生发展过程中发挥重要调控作用。表观遗传修饰是指DNA序列没有改变, 而基因表达却发生了可遗传的变化, 主要包括DNA甲基化和组蛋白修饰等。表观遗传为病原微生物与炎症反应间关系的研究架起了重要桥梁。炎症反应中T辅助细胞的分化, 细胞因子、趋化因子等基因的表达都受到表观遗传的调控。文章主要综述了DNA甲基化、组蛋白修饰等对炎症尤其是乳房炎的调控机制, 并就表观遗传调控在奶牛乳房炎治疗及抗病育种中的应用前景进行了展望。     

Defense Response to Pathogens Through Epigenetic Regulation in Rice

Epigenetic factors have recently emerged as key regulators of the defense response to pathogens in plants. The epigenetic mechanisms underlying defense regulation have been investigated mostly in Arabidopsis, while our understanding of the epigenetic regulation of defense in rice is limited. In this review, we summarize recent findings surrounding epigenetic mechanisms for defense in rice, primarily focusing on DNA methylation, histone modification, and small RNA regulation. In particular, we focused on RNA-directed DNA methylation (RdDM) and other epigenetic regulatory mechanisms that are involved in disease resistance. Finally, we explored potential epigenetic factors that might regulate the defense response in rice by analyzing available microarray data that can be used to uncover details of epigenetics regulation.     

Glial epigenetics in neuroinflammation and neurodegeneration

Epigenetic regulation shapes the differentiation and response to stimuli of all tissues and cells beyond what genetics would dictate. Epigenetic regulation acts through covalent modifications of DNA and histones while leaving the nucleotide code intact. However, these chromatin modifications are known to be vital components of the regulation of cell fate and response. With regards to the central nervous system (CNS), little is known about how epigenetic regulation shapes the function of neural cell types. The focus of research so far has been on epigenetic regulation of neuronal function and the role of epigenetics in tumorigenesis. However, the glial cell compartment, which makes up 90 % of all CNS cells, has so far received scant attention as to how epigenetics shape their differentiation and function. Here, we highlight current knowledge about epigenetic changes in glial cells occurring during CNS injury, neuroinflammatory conditions and neurodegenerative disease. This review offers an overview of the current understanding of epigenetic regulation in glial cells in CNS disease.     

DNA甲基化与miRNA相互调节与动脉粥样硬化

动脉粥样硬化是一类严重危害人类健康的心血管疾病,其发病机制一直是研究的热点.随着近年表观遗传学研究的深入,特别是人类表观基因组计划(Human Epigenome Project, HEP)的实施,以及国际人类表观基因组协会(Human Epigenome Con-sortium, HEC)的成立,DNA甲基化和miRNA在动脉粥样硬化中的调控作用机制被逐渐认识.它们不仅能够作为独立因子在动脉粥样硬化的发生发展过程发挥作用,而且最新研究发现,它们可以相互形成交叉网络调控,但其具体过程尚未阐明. 本文拟就DNA甲基化、miRNA在动脉粥样硬化发生发展中相互作用的最新研究进行综述.     

miRNAs的表达调控机制

microRNAs(miRNAs)是一类在转录后基因调控中发挥功能的非编码小RNAs,在发育、生长和分化等过程中发挥重要作用.至今已经在动物、植物和微生物等不同生物体中鉴定出来数千种miRNAs. miRNAs可以通过降解mRNA或抑制蛋白翻译的方式调节特异基因表达.生物体内约30%的基因都受miRNAs的调节.miRNAs的表达与功能受到转录因子、表观遗传学、多核苷酸多态性及其RNA编辑等多种因素的调节.此外,特异miRNA基因敲除的成功为研究miRNAs功能提供了有力的实验模型.     

Transcriptome analysis of age-related gain of callus-forming capacity in Arabidopsis hypocotyls

Callus-forming capacity is enhanced with hypocotyl maturity in Arabidopsis. However, the genetic regulation of age-related gain in capacity for callus formation is unclear. We used a gene expression microarray assay to characterize the underlying mechanisms during callus formation in young and mature hypocotyl explants of Arabidopsis. As expected, genes involved in photosynthesis and cell wall thickening showed altered expression during hypocotyl maturation. In addition, genes involved in cytokinin perception were enriched in mature hypocotyl tissues. Phytohormone-induced callus formation in hypocotyl explants was accompanied by increased expression of genes mainly related to the cell cycle, histones and epigenetics. The induction level of these genes was higher in mature hypocotyl explants than young explants during callus formation. We identified a number of genes, including those with unknown function, potentially involved in age-related gain in callus formation. Our results provide insight into the effect of hypocotyl age on callus formation. Altered cytokinin signaling components, cell cycle regulation and epigenetics may work in concert to lead to gain of callus-forming capacity in hypocotyls with age.     

表观遗传学及其研究方法

表观遗传学是一门重要的生命学科,主要包括DNA的甲基化、组蛋白修饰以及非编码RNA等内容,其中任何一方面的表观遗传学变化对生物体的生命过程都有重要的影响。近年来随着生命科学的快速发展,表观遗传学越来越受到人们的关注,各种先进科技的应用也使得表观遗传学实验技术得到快速的发展。本文对DNA甲基化、组蛋白修饰及非编码RNA的基本内容及实验方法进行了综述,并对不同的研究方法进行分析,有利于表观遗传学的深入研究。     

长链非编码RNA与表观遗传调控

近年来,表观遗传学(epigenetics)备受关注.表观遗传调控的方式主要包括DNA甲基化、组蛋白修饰和染色质重塑等.ENCODE计划及随后的研究发现,人类基因组中仅有很小一部分DNA序列负责编码蛋白质,而其余大部分被转录为非编码RNA(non-codingRNA,ncRNA).其中长链非编码RNA(long non-codingRNA,lncRNA)是一类长度大于200nt并且缺乏蛋白质编码能力的RNA分子.越来越多的研究表明,lncRNAs能够通过表观遗传调控、转录调控以及转录后调控等多个层面调节基因的表达,从而参与细胞增殖、分化和凋亡等多种生物学过程.本文将着重综述lncRNAs在表观遗传调控中的作用及其最新的研究进展.     

胎盘发生中的表观遗传学

胚外组织尤其是胎盘的正常发生对于维持哺乳动物胎儿在子宫中的发育和生长是必须的。胎盘发生是一个复杂的基因表达调控的过程,近年来的研究表明表观遗传在该过程中也起着重要作用。表观遗传调控在胎盘发生过程的几个主要事件中发挥作用,包括表观遗传对滋养层细胞分化和发育的调控、印记基因对胎盘发生和营养转运的调控、胎盘中的X染色体失活,以及胎盘表观遗传调控异常所导致的妊娠相关疾病。