Epigenetics

Emerging evidence is shedding light on a large and complex network of epigenetic modifications at play in human stem cells. This “epigenetic landscape” governs the fine-tuning and precision of gene expression programs that define the molecular basis of stem cell pluripotency, differentiation and reprogramming. This review will focus on recent progress in our understanding of the processes that govern this landscape in stem cells, such as histone modification, DNA methylation, alterations of chromatin structure due to chromatin remodeling and non-coding RNA activity. Further investigation into stem cell epigenetics promises to provide novel advances in the diagnosis and treatment of a wide array of human diseases.     

Epigenetics: Judge,jury and executioner of stem cell fate

Emerging evidence is shedding light on a large and complex network of epigenetic modifications at play in human stem cells. This “epigenetic landscape” governs the fine-tuning and precision of gene expression programs that define the molecular basis of stem cell pluripotency, differentiation and reprogramming. This review will focus on recent progress in our understanding of the processes that govern this landscape in stem cells, such as histone modification, DNA methylation, alterations of chromatin structure due to chromatin remodeling and non-coding RNA activity. Further investigation into stem cell epigenetics promises to provide novel advances in the diagnosis and treatment of a wide array of human diseases.     

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.     

DNA损伤修复过程表观遗传学改变

多种化学、物理及生物因素可诱发细胞DNA损伤,损伤后DNA损伤位点被相关损伤感受器识别,激活相应的修复通路进行DNA修复。越来越多的证据表明DNA甲基化状态、蛋白翻译后修饰、染色质重塑、miRNA等修饰方式参与了DNA的损伤修复。文章通过不同损伤修复通路中这些修饰的特点,阐述表观遗传学改变在DNA损伤修复发展过程中的作用机制。     

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...     

Epigenetics and chromatin plasticity in embryonic stem cells

The study of embryonic stem cells is in the spotlight in many laboratories that study the structure and function of chromatin and epigenetic processes. The key properties of embryonic stem cells are their capacity for self-renewal and their pluripotency. Pluripotent stem cells are able to differentiate into the cells of all three germ layers, and because of this property they represent a promising therapeutic tool in the treatment of diseases such as Parkinson’s disease and diabetes, or in the healing of lesions after heart attack. As the basic nuclear unit, chromatin is responsible for the regulation of the functional status of cells, including pluripotency and differentiation. Therefore, in this review we discuss the functional changes in chromatin during differentiation and the correlation between epigenetics events and the differentiation potential of embryonic stem cells. In particular we focus on post-translational histone modification, DNA methylation and the heterochromatin protein HP1 and its unique function in mouse and human embryonic stem cells.     

黑色素瘤发生发展中的表观遗传学调控

人恶性黑色素瘤(malignant melanoma)是近年来高发病率和高死亡率的肿瘤之一.目前尚缺乏有效的治疗方法.而表观遗传如DNA甲基化(DNA methylation)、组蛋白修饰(histonemodification)、染色质重塑(chromatin remodeling)及RNA干扰(RNA interference,RNAi)等改变在人黑色素瘤的发生、发展和转移中有重要作用.阐明黑色素瘤发生发展的表观遗传学机制已引起了学者的普遍关注.本文综述了人类黑色素瘤发生发展中所特异的表观遗传改变:CpG岛的异常甲基化修饰、组蛋白甲基化和乙酰化修饰、染色质重塑以及microRNA在黑色素瘤发生和转移中的作用,并对应用表观遗传修饰治疗人类黑色素瘤进行了探讨.     

Epigenetic modifications of histones during osteoblast differentiation

In bone biology, epigenetics plays a key role in mesenchymal stem cells' (MSCs) commitment towards osteoblasts. It involves gene regulatory mechanisms governed by chromatin modulators. Predominant epigenetic mechanisms for efficient osteogenic differentiation include DNA methylation, histone modifications, and non-coding RNAs. Among these mechanisms, histone modifications critically contribute to altering chromatin configuration. Histone based epigenetic mechanisms are an essential mediator of gene expression during osteoblast differentiation as it directs the bivalency of the genome. Investigating the importance of histone modifications in osteogenesis may lead to the development of epigenetic-based remedies for genetic disorders of bone. Hence, in this review, we have highlighted the importance of epigenetic modifications such as post-translational modifications of histones, including methylation, acetylation, phosphorylation, ubiquitination, and their role in the activation or suppression of gene expression during osteoblast differentiation. Further, we have emphasized the future advancements in the field of epigenetics towards orthopaedical therapeutics.     

Epigenetic regulation of immune escape genes in cancer

According to the concept of immune surveillance, the appearance of a tumor indicates that it has earlier evaded host defenses and subsequently must have escaped immunity to evolve into a full-blown cancer. Tumor escape mechanisms have focused mainly on mutations of immune and apoptotic pathway genes. However, data obtained over the past few years suggest that epigenetic silencing in cancer may be as frequent a cause of gene inactivation as are mutations. Here, we discuss the evidence that tumor immune evasion is mediated by non-mutational epigenetic events involving chromatin and that epigenetics collaborates with mutations in determining tumor progression. Since epigenetic changes are potentially reversible, the relative contribution of mutations and epigenetics, to the gene defects in any given tumor, may be a factor in determining the efficacy of treatments. We review new developments in basic chromatin mechanisms and in this context describe the rationale for the current use of epigenetic agents in cancer therapy and for a novel epigenetically generated tumor vaccine model. We emphasize that epigenetic cancer treatments are currently a ‘blunt-sword’ and suggest future directions for designing chromatin-based programs of potential value in the diagnosis and treatment of cancer.     

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.     

重性抑郁障碍发病的表观遗传调控假说

表观遗传学是研究主要受控于DNA甲基化、染色质结构变化的可遗传和逆转的基因组功能的调控。近年来, 越来越多的证据表明表观遗传因素在精神分裂症、双相障碍、药物成瘾等重性精神障碍的发病中扮演着重要角色。文章综述了表观遗传现象的分子机制, 介绍了表观遗传修饰与复杂性疾病的关系, 并在此基础上对重性抑郁障碍(Major depressive disorder, MDD)发病的表观遗传调控假说及最新研究进展进行了总结。     

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.     

Epigenetic events in mammalian germ-cell development: reprogramming and beyond

The epigenetic profile of germ cells, which is defined by modifications of DNA and chromatin, changes dynamically during their development. Many of the changes are associated with the acquisition of the capacity to support post-fertilization development. Our knowledge of this aspect has greatly increased- for example, insights into how the re-establishment of parental imprints is regulated. In addition, an emerging theme from recent studies is that epigenetic modifiers have key roles in germ-cell development itself--for example, epigenetics contributes to the gene-expression programme that is required for germ-cell development, regulation of meiosis and genomic integrity. Understanding epigenetic regulation in germ cells has implications for reproductive engineering technologies and human health.     

New insights into plant somatic embryogenesis: an epigenetic view

Somatic embryogenesis plays a significant role in plant regeneration and requires complex cellular, molecular, and biochemical processes for embryo initiation and development associated with plant epigenetics. Epigenetic regulation encompasses many sensitive events and plays a vital role in gene expression through DNA methylation, chromatin remodelling, and small RNAs. Recently, regulation of epigenetic mechanisms has been recognized as the most promising occurrences during somatic embryogenesis in plants. A few reports demonstrated that the level of DNA methylation can alter in embryogenic cells under in vitro environments. Changes or modification in DNA methylation patterns is linked with regulatory mechanisms of various candidate marker genes, involved in the initiation and development of somatic embryogenesis in plants. This review summarizes the current scenario of the role of epigenetic mechanisms as candidate markers during somatic embryogenesis. It also delivers a comprehensive and systematic analysis of more recent discoveries on expression of embryogenic-regulating genes during somatic embryogenesis, epigenetic variation. Biotechnological applications of epigenetics as well as new opportunities or future perspectives in the development of somatic embryogenesis studies are covered. Further research on such strategies may serve as exciting interaction models of epigenetic regulation in plant embryogenesis and designing novel approaches for plant productivity and crop improvement at molecular levels.