A methylation rendezvous: reader meets writers

It is well established that two marks of silent chromatin, DNA methylation and histone H3 methylation at lysine 9, engage in an epigenetic conversation. In a recent issue of Genes & Development, Smallwood et al. (2007) report that the mammalian HP1 adaptor "translates" methylation information from histone to DNA, helping to cement epigenetic expression states.     

Epigenetics in Alzheimer’s Disease: Perspective of DNA Methylation

Research over the years has shown that causes of Alzheimer’s disease are not well understood, but over the past years, the involvement of epigenetic mechanisms in the developing memory formation either under pathological or physiological conditions has become clear. The term epigenetics represents the heredity of changes in phenotype that are independent of altered DNA sequences. Different studies validated that cytosine methylation of genomic DNA decreases with age in different tissues of mammals, and therefore, the role of epigenetic factors in developing neurological disorders in aging has been under focus. In this review, we summarized and reviewed the involvement of different epigenetic mechanisms especially the DNA methylation in Alzheimer’s disease (AD), late-onset Alzheimer’s disease (LOAD), familial Alzheimer’s disease (FAD), and autosomal dominant Alzheimer’s disease (ADAD). Down to the minutest of details, we tried to discuss the methylation patterns like mitochondrial DNA methylation and ribosomal DNA (rDNA) methylation. Additionally, we mentioned some therapeutic approaches related to epigenetics, which could provide a potential cure for AD. Moreover, we reviewed some recent studies that validate DNA methylation as a potential biomarker and its role in AD. We hope that this review will provide new insights into the understanding of AD pathogenesis from the epigenetic perspective especially from the perspective of DNA methylation.     

Computer- and structure-based lead design for epigenetic targets

The term epigenetics is defined as inheritable changes that influence the outcome of a phenotype without changes in the genome. Epigenetics is based upon DNA methylation and posttranslational histone modifications. While there is much known about reversible acetylation as a posttranslational modification, research on reversible histone methylation is still emerging, especially with regard to drug discovery. As aberrant epigenetic modifications have been linked to many diseases, inhibitors of histone modifying enzymes are very much in demand. This article will summarize the progress on small molecule epigenetic inhibitors identified by structure- and computer-based approaches.     

Holding on through DNA Replication: Histone Modification or Modifier?

Histone methylation is widely believed to contribute to epigenetic inheritance by persevering through DNA replication and subsequently templating methylation of daughter chromosome regions. However, a report in this issue (Petruk et?al.) suggests that chromatin association of the methytransferase complexes themselves persists through replication and re-establishes histone methylation.     

A truly ecological epigenetics study

Until a few years ago, epigenetics was a field of research that had nothing to do with ecology and that virtually no ecologist had ever heard of. This is now changing, as more and more ecologists learn about epigenetic processes and their potential ecological and evolutionary relevance, and a new research field of ecological epigenetics is beginning to take shape. One question that is particularly intriguing ecologists is to what extent epigenetic variation is an additional, and hitherto overlooked, source of natural variation in ecologically important traits. In this issue of Molecular Ecology, Herrera & Bazaga (2011) provide one of the first attempts to truly address this question in an ecological setting. They study variation of DNA methylation in a wild population of the rare, long-lived violet Viola cazorlensis, and they use these data to explore interrelations between environmental, genetic and epigenetic variation, and in particular the extent to which these factors are related to long-term differences in herbivore damage among plants. They find substantial epigenetic variation among plant individuals. Interestingly, this epigenetic variation is significantly correlated with long-term differences in herbivory, but only weakly with herbivory-related DNA sequence variation, which suggests that besides habitat, substrate and genetic variation, epigenetic variation may be an additional, and at least partly independent, factor influencing plant–herbivore interactions in the field. Although the study by Herrera & Bazaga (2011) raises at least as many new questions as it answers, it is a pioneering example of how epigenetics can be incorporated into ecological field studies, and it illustrates the value and potential novel insights to be gained from such efforts.     

Cancer epigenetics reaches mainstream oncology

Epigenetics is one of the most promising and expanding fields in the current biomedical research landscape. Since the inception of epigenetics in the 1940s, the discoveries regarding its implications in normal and disease biology have not stopped, compiling a vast amount of knowledge in the past decade. The field has moved from just one recognized marker, DNA methylation, to a variety of others, including a wide spectrum of histone modifications. From the methodological standpoint, the successful initial single gene candidate approaches have been complemented by the current comprehensive epigenomic approaches that allow the interrogation of genomes to search for translational applications in an unbiased manner. Most important, the discovery of mutations in the epigenetic machinery and the approval of the first epigenetic drugs for the treatment of subtypes of leukemias and lymphomas has been an eye-opener for many biomedical scientists and clinicians. Herein, we will summarize the progress in the field of cancer epigenetics research that has reached mainstream oncology in the development of new biomarkers of the disease and new pharmacological strategies.     

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。     

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.     

Dad’s Snoring May Have Left Molecular Scars in Your DNA: the Emerging Role of Epigenetics in Sleep Disorders

The sleep-wake cycle is a biological phenomena under the orchestration of neurophysiological, neurochemical, neuroanatomical, and genetical mechanisms. Moreover, homeostatic and circadian processes participate in the regulation of sleep across the light–dark period. Further complexity of the understanding of the genesis of sleep engages disturbances which have been characterized and classified in a variety of sleep–wake cycle disorders. The most prominent sleep alterations include insomnia as well as excessive daytime sleepiness. On the other side, several human diseases have been linked with direct changes in DNA, such as chromatin configuration, genomic imprinting, DNA methylation, histone modifications (acetylation, methylation, ubiquitylation or sumoylation, etc.), and activating RNA molecules that are transcribed from DNA but not translated into proteins. Epigenetic theories primarily emphasize the interaction between the environment and gene expression. According to these approaches, the environment to which mammals are exposed has a significant role in determining the epigenetic modifications occurring in chromosomes that ultimately would influence not only development but also the descendants’ physiology and behavior. Thus, what makes epigenetics intriguing is that, unlike genetic variation, modifications in DNA are altered directly by the environment and, in some cases, these epigenetic changes may be inherited by future generations. Thus, it is likely that epigenetic phenomena might contribute to the homeostatic and/or circadian control of sleep and, possibly, have an undescribed link with sleep disorders. An exciting new horizon of research is arising between sleep and epigenetics since it represents the relevance of the study of how the genome learns from its experiences and modulates behavior, including sleep.     

A crack in histone lysine methylation

Histone lysine methylation is regarded as a very stable modification with important functions in epigenetic gene control and for organizing chromatin domains. While more robust modifications of the chromatin template are essential to stabilize epigenetic information, there is now the first evidence for a histone lysine demethylase that reverts an activating methyl mark to the unmodified state (Shi et al., 2004 [this issue of Cell]).     

The Russian Biological Student Microscopes

Our out-of-school practical exercise was designed to bring upper secondary school students in contact with one of the most exciting and expanding topics in biology today: epigenetics. In school, students only study the basics in genetics and the respective investigation techniques as provided by the syllabus. For a practical exercise in epigenetics, however, they need additional knowledge. Hence, they are introduced to the subject of epigenetics and its molecular mechanisms. Students are asked to examine the different DNA methylation conditions of lambda DNA using both a restriction assay and gel electrophoresis in an out-of-school laboratory. DNA methylation is one of the major epigenetic mechanisms which have significant effects on gene expression; studies on monozygotic twins have shown that it is influenced by the environment. This exercise enables students to correctly identify the different methylation conditions of distributed lambda DNA samples. In doing so, they receive a first introduction to one epigenetic mechanism. The necessity for students to experience science in out-of-school settings has been shown by several scholars. The practical exercise we are proposing in this article was elaborated for such learning opportunities for upper secondary students to gain insight into contemporary science issues.     

ZFP57: KAPturing DNA methylation at imprinted loci

In this issue of Molecular Cell, Quenneville et al. (2011) characterize the role of ZFP57 in the maintenance of DNA methylation at imprinting control regions (ICRs), revealing an allele-specific binding pattern, binding motif, and interactions with other epigenetic regulators.     

肿瘤表观基因组学研究进展

多年来遗传学改变一直是肿瘤研究的焦点,近来人们越来越认识到异常表观遗传修饰在肿瘤形成中所起的重要作用。表观遗传修饰包括DNA甲基化、组蛋白修饰等,其变异会导致基因转录异常。表观基因组学是在基因组水平上对表观遗传学改变的研究。文章主要介绍目前已知的肿瘤表观基因组学相关内容,阐述表观遗传修饰与肿瘤的紧密关系及异常表观遗传修饰作为生物标记在肿瘤诊断、预后及治疗方面的最新研究进展。     

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.     

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.     

DNA methylation in embryonic stem cells

Embryonic stem cells (ESCs) are pluripotent, self‐renewing cells. These cells can be used in applications such as cell therapy, drug development, disease modeling, and the study of cellular differentiation. Investigating the interplay of epigenetics, genetics, and gene expression in control of pluripotence and differentiation could give important insights on how these cells function. One of the best known epigenetic factors is DNA methylation, which is a major mechanism for regulation of gene expression. This phenomenon is mostly seen in imprinted genes and X‐chromosome inactivation where DNA methylation of promoter regions leads to repression of gene expression. Differential DNA methylation of pluripotence‐associated genes such as Nanog and Oct4/Pou5f1 has been observed between pluripotent and differentiated cells. It is clear that tight regulation of DNA methylation is necessary for normal development. As more associations between aberrant DNA methylation and disease are reported, the demand for high‐throughput approaches for DNA methylation analysis has increased. In this article, we highlight these methods and discuss recent DNA methylation studies on ESCs. J. Cell. Biochem. 109: 1–6, 2010. © 2009 Wiley‐Liss, Inc.     

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.     

MEDEA takes control of its own imprinting

Genomic imprinting is an essential epigenetic process that controls the size of seeds in flowering plants. In Arabidopsis, DEMETER activates the maternal copy of the imprinted MEDEA Polycomb gene. In this issue of Cell, Gehring et al. (2006) demonstrate that this activation involves DNA demethylation of MEDEA by DEMETER. Remarkably, they also find that silencing of the paternal MEDEA allele is independent of DNA methylation and is controlled by maternal expression of MEDEA itself.     

表观遗传调节在神经发育中的生理及病理学意义初探

表观遗传学(epigenetics)研究的是调控遗传物质表达而不改变遗传基因DNA序列所引起的表型变化的过程及其机制。这种变化在细胞生命周期中始终存在,并在数代繁衍过程中保持不变。表观遗传调控过程十分复杂,主要包括DNA甲基化(methylation)、组蛋白修饰(histone modifica-tion)、染色质重塑(chromatin remodeling)、基因印迹(gene imprinting)等,其中DNA甲基化是最为经典的表观遗传调控方式之一,对其了解也最多。本文着重探讨表观遗传调节在神经发育过程中的生理、病理学意义及其分子机制。