A new genetics or an epiphenomenon? Variations in the discourse of epigenetics researchers

Epigenetics is a field on the rise that seeks to explain phenotypic variance despite a stable and enduring DNA sequence. The hopes for the field are high, and claims about its revolutionary potential abound. Some scholars in the humanities and social sciences see the field as potentially replacing reductionism and genetic determinism, bringing social life and environment more firmly into view. This paper attends to the discourses of epigenetics researchers themselves. Through qualitative interviewing and analysis, I classify these scientists into three groups based on the claims they make about the impact and future of their field: champions, those who take the middle ground, and skeptics. The variance in discourse about epigenetics suggests a far more complex and contested trajectory for the field, one that may or may not support anti-deterministic views.     

Novel epigenetic therapeutic strategies and targets in cancer

The critical role of dysregulated epigenetic pathways in cancer genesis, development, and therapy has typically been established as a result of scientific and technical innovations in next generation sequencing. RNA interference, histone modification, DNA methylation and chromatin remodelling are epigenetic processes that control gene expression without causing mutations in the DNA. Although epigenetic abnormalities are thought to be a symptom of cell tumorigenesis and malignant events that impact tumor growth and drug resistance, physicians believe that related processes might be a key therapeutic target for cancer treatment and prevention due to the reversible nature of these processes. A plethora of novel strategies for addressing epigenetics in cancer therapy for immuno-oncological complications are currently available - ranging from basic treatment to epigenetic editing. – and they will be the subject of this comprehensive review. In this review, we cover most of the advancements made in the field of targeting epigenetics with special emphasis on microbiology, plasma science, biophysics, pharmacology, molecular biology, phytochemistry, and nanoscience.     

Epigenetic metaphors: an interdisciplinary translation of encoding and decoding

Looking at the new and often disputed science of epigenetics, we examined the challenges faced by scientists when they communicate scientific research to the public. We focused on the use of metaphors to illustrate notions of epigenetics and genetics. We studied the “encoding” by epigeneticists and “decoding” in focus groups with diverse backgrounds. We observed considerable overlap in the dominant metaphors favored by both researchers and the lay public. However, the groups differed markedly in their interpretations of which metaphors aided understanding or not. We conclude by discussing the role of metaphors and their interpretations in the context of a shift from pre-deterministic genomic metaphors to more active, dynamic and nuanced epigenetic metaphors. These reflections on the choice of metaphors and differences in encoding/decoding are important for science communication and scientific boundary-maintenance.     

Epigenetics for the social sciences: justice,embodiment, and inheritance in the postgenomic age

In this paper, I firstly situate the current rise of interest in epigenetics in the broader history of attempts to go “beyond the gene” in twentieth-century biology. In the second part, after a summary of the main differences between epigenetic and genetic mutations, I consider what kind of implications the sui generis features of epigenetic mutations may have for the social sciences. I focus in particular on two sites of investigation: (a) the blurring of the boundaries between natural and social inequalities in theories of justice and their possible implications for public policy and public health and (b) a deepening of the notion that the constitution of the body is deeply dependent on its material and socially shaped surroundings (“embodied constructivism”). In conclusion, I advance some cautionary reflections on some of the (known and unprecedented) problems that the circulation of epigenetics in wider society may present.     

Neural and behavioral epigenetics; what it is,and what is hype

The ability to examine epigenetic mechanisms in the brain has become readily available over the last 20 years. This has led to an explosion of research and interest in neural and behavioral epigenetics. Of particular interest to researchers, and indeed the lay public, is the possibility that epigenetic processes, such as changes in DNA‐methylation and histone modification, may provide a biochemical record of environmental effects. This has led to some fascinating insights into how molecular changes in the brain can control behavior. However, some of this research has also attracted controversy and, as is dealt with here, some overblown claims. This latter problem is partly linked to the shifting sands of what is defined as ‘epigenetics’. In this review, I provide an overview of what exactly epigenetics is, and what is hype, with the aim of opening up a debate as to how this exciting field moves forward.     

An ecologist's guide for studying DNA methylation variation in wild vertebrates

The field of molecular biology is advancing fast with new powerful technologies, sequencing methods and analysis software being developed constantly. Commonly used tools originally developed for research on humans and model species are now regularly used in ecological and evolutionary research. There is also a growing interest in the causes and consequences of epigenetic variation in natural populations. Studying ecological epigenetics is currently challenging, especially for vertebrate systems, because of the required technical expertise, complications with analyses and interpretation, and limitations in acquiring sufficiently high sample sizes. Importantly, neglecting the limitations of the experimental setup, technology and analyses may affect the reliability and reproducibility, and the extent to which unbiased conclusions can be drawn from these studies. Here, we provide a practical guide for researchers aiming to study DNA methylation variation in wild vertebrates. We review the technical aspects of epigenetic research, concentrating on DNA methylation using bisulfite sequencing, discuss the limitations and possible pitfalls, and how to overcome them through rigid and reproducible data analysis. This review provides a solid foundation for the proper design of epigenetic studies, a clear roadmap on the best practices for correct data analysis and a realistic view on the limitations for studying ecological epigenetics in vertebrates. This review will help researchers studying the ecological and evolutionary implications of epigenetic variation in wild populations.     

Investigating the evolution and development of biological complexity under the framework of epigenetics

Biological complexity is a key component of evolvability, yet its study has been hampered by a focus on evolutionary trends of complexification and inconsistent definitions. Here, we demonstrate the utility of bringing complexity into the framework of epigenetics to better investigate its utility as a concept in evolutionary biology. We first analyze the existing metrics of complexity and explore the link between complexity and adaptation. Although recently developed metrics allow for a unified framework, they omit developmental mechanisms. We argue that a better approach to the empirical study of complexity and its evolution includes developmental mechanisms. We then consider epigenetic mechanisms and their role in shaping developmental and evolutionary trajectories, as well as the development and organization of complexity. We argue that epigenetics itself could have emerged from complexity because of a need to self‐regulate. Finally, we explore hybridization complexes and hybrid organisms as potential models for studying the association between epigenetics and complexity. Our goal is not to explain trends in biological complexity but to help develop and elucidate novel questions in the investigation of biological complexity and its evolution.     

外因遗传学及其重要意义

本文综述外因遗传学的提出、发展的各个主要阶段和该学科的确立。基因特性可以从两个层面来进行研究,（1）是遗传物质的传递,（2）是从基因型到表型这个过程。外因遗传学从1942年沃丁顿提出,经1987年霍利迪的发展,到现今在各类生物包括人类中积累了丰富的资料,并能够用化学分子来说明其作用机理。外因遗传学现代的定义为：基因功能的改变,凡未牵涉到DNA的序列,又可通过细胞的有丝或减数分裂而遗传者,称为外因遗传。作者介绍了外因遗传的范围,如：X染色体剂量补偿、基因组印记、分化细胞的基因组重新编程、癌基因、转录的分子调节、RNA介导的基因沉默、组蛋白码、着丝粒的遗传和进化以及外因遗传的进化。此外,还有科学界的反应和评价,包括其在人类生物学和医学方面的重要性和该理论的重大的意义。组蛋白码不同于DNA码,DNA码需要精确拷贝,而且是静止的;而外因遗传就不是如此之僵硬,而具有一定的弹性,因为组蛋白码是决定于其上下文的,可在不同场景下组合成不同的码,它是为其他的蛋白质所读的。遗传需要稳定性,也需要根据内因和外因的变化而有灵活性,DNA码和组蛋白码相辅相成,对复杂的生物是必备的。 The Meaning of Epigenetics HU Kai The Tropical Biology Center,Hainan University,Haikou,Hainan 570028,China Abstract:Epigenetics,the term was introduced by Conrad H.Waddington,in 1942,he said that to compare genetics with epigenetics,the study of the processes by which genotype gives rise to phenotype.In 1987,Robin Holliday redefined epigenetic as “Nuclear inheritance which is not based on differences in DNA sequence”.The author of this paper introduced that in Science,10 August 2001,there was a special collection of review articles focused on the topic of epigenetics.The new “histone code” hypothesis states that the highly modifiable amino termini could carry their own combinatorial codes to help control phenotype,and that part of this code is heritable.And in light of this hypothesis,researchers are approaching further possibilities in human biology and types of cancer and other diseases. Key words：epigenetics; gene expressing     

Mapping the new molecular landscape: social dimensions of epigenetics

Epigenetics is the study of changes in gene expression caused by mechanisms other than changes in the DNA itself. The field is rapidly growing and being widely promoted, attracting attention in diverse arenas. These include those of the social sciences, where some researchers have been encouraged by the resonance between imaginaries of development within epigenetics and social theory. Yet, sustained attention from science and technology studies (STS) scholars to epigenetics and the praxis it propels has been lacking. In this article, we reflexively consider some of the ways in which epigenetics is being constructed as an area of biomedical novelty and discuss the content and logics underlying the ambivalent promises being made by scientists working in this area. We then reflect on the scope, limits and future of engagements between epigenetics and the social sciences. Our discussion is situated within wider literatures on biomedicine and society, the politics of “interventionist STS”, and on the problems of “caseness” within empirical social science.     

Ecological plant epigenetics: Evidence from model and non‐model species,and the way forward

Growing evidence shows that epigenetic mechanisms contribute to complex traits, with implications across many fields of biology. In plant ecology, recent studies have attempted to merge ecological experiments with epigenetic analyses to elucidate the contribution of epigenetics to plant phenotypes, stress responses, adaptation to habitat, and range distributions. While there has been some progress in revealing the role of epigenetics in ecological processes, studies with non‐model species have so far been limited to describing broad patterns based on anonymous markers of DNA methylation. In contrast, studies with model species have benefited from powerful genomic resources, which contribute to a more mechanistic understanding but have limited ecological realism. Understanding the significance of epigenetics for plant ecology requires increased transfer of knowledge and methods from model species research to genomes of evolutionarily divergent species, and examination of responses to complex natural environments at a more mechanistic level. This requires transforming genomics tools specifically for studying non‐model species, which is challenging given the large and often polyploid genomes of plants. Collaboration among molecular geneticists, ecologists and bioinformaticians promises to enhance our understanding of the mutual links between genome function and ecological processes.     

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.     

The marbled crayfish: a new model organism for research on development, epigenetics and evolutionary biology

Model organisms have contributed significantly to the understanding of basic biological phenomena. Suitable animal models are at hand for some research disciplines like genetics, development and cell biology but are still sought after for others like epigenetics. Research of the last years has revealed that the marbled crayfish (Marmorkrebs), which was discovered in the mid-1990s, meets researchers' demands for a vigorous, genetically identical and eurytopic laboratory model very well. Its most prominent advantages are production of high numbers of genetically identical offspring, stepwise alteration of the phenotype by moulting, complex morphology and behaviour and sequential generation of segments and limbs. This paper first reviews the discovery and research history of the marbled crayfish, its biology and culture and its special advantages. It then discusses, based on the published data, its suitability as a laboratory model for various research disciplines. The greatest potential of the marbled crayfish lies in epigenetics and environmental epigenomics and in stem cell research and regeneration. The marbled crayfish also appears to be suitable for the investigation of the role of stochastic developmental variation and epigenetic inheritance in evolution and to contribute to evo-devo and eco-devo. This unique crayfish is even of some value for applied biologists, for example as a toxicological test species.     

Epigenetic regulation of development and pathogenesis in fungal plant pathogens

Evidently, epigenetics is at forefront in explaining the mechanisms underlying the success of human pathogens and in the identification of pathogen‐induced modifications within host plants. However, there is a lack of studies highlighting the role of epigenetics in the modulation of the growth and pathogenicity of fungal plant pathogens. In this review, we attempt to highlight and discuss the role of epigenetics in the regulation of the growth and pathogenicity of fungal phytopathogens using Magnaporthe oryzae, a devastating fungal plant pathogen, as a model system. With the perspective of wide application in the understanding of the development, pathogenesis and control of other fungal pathogens, we attempt to provide a synthesized view of the epigenetic studies conducted on M. oryzae to date. First, we discuss the mechanisms of epigenetic modifications in M. oryzae and their impact on fungal development and pathogenicity. Second, we highlight the unexplored epigenetic mechanisms and areas of research that should be considered in the near future to construct a holistic view of epigenetic functioning in M. oryzae and other fungal plant pathogens. Importantly, the development of a complete understanding of the modulation of epigenetic regulation in fungal pathogens can help in the identification of target points to combat fungal pathogenesis.     

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.     

Frontiers in the bioarchaeology of stress and disease: Cross-disciplinary perspectives from pathophysiology,human biology,and epidemiology

Over the last four decades, bioarchaeology has experienced significant technical growth and theoretical maturation. Early 21st century bioarchaeology may also be enhanced from a renewed engagement with the concept of biological stress. New insights on biological stress and disease can be gained from cross-disciplinary perspectives regarding human skeletal variation and disease. First, pathophysiologic and molecular signaling mechanisms can provide more precise understandings regarding formation of pathological phenotypes in bone. Using periosteal new bone formation as an example, various mechanisms and pathways are explored in which new bone can be formed under conditions of biological stress, particularly in bone microenvironments that involve inflammatory changes. Second, insights from human biology are examined regarding some epigenetic factors and disease etiology. While epigenetic effects on stress and disease outcomes appear profoundly influential, they are mostly invisible in skeletal tissue. However, some indirect and downstream effects, such as the developmental origins of adult health outcomes, may be partially observable in bioarchaeological data. Emerging perspectives from the human microbiome are also considered. Microbiomics involves a remarkable potential to understand ancient biology, disease, and stress. Third, tools from epidemiology are examined that may aid bioarchaeologists to better cope with some of the inherent limitations of skeletal samples to better measure and quantify the expressions of skeletal stress markers. Such cross-disciplinary synergisms hopefully will promote more complete understandings of health and stress in bioarchaeological science. Am J Phys Anthropol 155:294–308, 2014. © 2014 Wiley Periodicals, Inc.     

Metaphors in search of a target: the curious case of epigenetics

Carrying out research in genetics and genomics and communicating about them would not be possible without metaphors such as “information,” “code,” “letter” or “book.” Genetic and genomic metaphors have remained relatively stable for a long time but are now beginning to shift in the context of synthetic biology and epigenetics. This article charts the emergence of metaphors in the context of epigenetics, first through collecting some examples of metaphors in scientific and popular writing and second through a systematic analysis of metaphors used in two UK broadsheets. Findings show that while source domains for metaphors can be identified, such as our knowledge of electrical switches or of bookmarks, it is difficult to pinpoint target domains for such metaphors. This may be indicative both of struggles over what epigenetics means for scientists (natural and social) and of difficulties associated with talking about this, as yet, young field in the popular press.     

DNA Methylation and Epigenotypes

The science of epigenetics is the study of all those mechanisms that control the unfolding of the genetic program for development and determine the phenotypes of differentiated cells. The pattern of gene expression in each of these cells is called the epigenotype. The best known and most thoroughly studied epigenetic mechanism is DNA methylation, which provides a basis both for the switching of gene activities, and the maintenance of stable phenotypes. The human epigenome project is the determination of the pattern of DNA methylation in multiple cell types. Some methylation sites, such as those in repeated genetic elements, are likely to be the same in all cell types, but genes with specialized functions will have distinct patterns of DNA methylation. Another project for the future is the study of the reprogramming of the genome in gametogenesis and early development. Much is already known about the de novo methylation of tumor suppressor genes in cancer cells, but the significance of epigenetic defects during ageing and in some familial diseases remains to be determined.     

What obesity research tells us about epigenetic mechanisms

The pathophysiology of obesity is extremely complex and is associated with extensive gene expression changes in tissues throughout the body. This situation, combined with the fact that all gene expression changes are thought to have associated epigenetic changes, means that the links between obesity and epigenetics will undoubtedly be vast. Much progress in identifying epigenetic changes induced by (or inducing) obesity has already been made, with candidate and genome-wide approaches. These discoveries will aid the clinician through increasing our understanding of the inheritance, development and treatment of obesity. However, they are also of great value for epigenetic researchers, as they have revealed mechanisms of environmental interactions with epigenetics that can produce or perpetuate a disease state. Here, we will review the evidence for four mechanisms through which epigenetics contributes to obesity: as downstream effectors of environmental signals; through abnormal global epigenetic state driving obesogenic expression patterns; through facilitating developmental programming and through transgenerational epigenetic inheritance.     

CpG Island Hypermethylation of Tumor Suppressor microRNAs in Human Cancer

In the last few years, microRNAs have started a revolution in molecular biology and emerged as key players in the cancer process. For these reasons, it is extremely important to understand the physiological and disease-associated mechanisms underlying the regulation of these small, single-stranded RNAs. Thus, it was merely a matter of time before microRNAs and epigenetics coincided. In cancer, aberrant DNA hypermethylation of tumor suppressor genes, global genomic DNA hypomethylation, and disruption of the histone modification patterns are the main epigenetic alterations, and have consequently been widely studied. Some microRNAs are downregulated in cancer and act as bona fide tumor suppressor genes, and this knowledge led to the proposal of the hypothesis that miRNAs could be silenced by epigenetic mechanisms. It has recently been shown that miR-127 and miR-124a, two putative tumor suppressor miRNAs, are methylated in tumor cells. Epigenomic tools can be effectively used in the search for new methylated tumor suppressor microRNAs. Furthermore, this aberrant methylation can be reversed by epigenetic drugs, such as DNA demethylating agents and histone deacetylase inhibitors, restoring microRNA expression levels and reverting the tumoral phenotype. In the coming years we will come to realize more fully the relevance of this expected encounter between two forces – epigenetics and microRNAs – that are currently at the forefront of biology.