Chromatin remodelling

Epigenetic mechanisms are heritable traits that are mediated by changes in a genetic locus that do not involve a modification at the nucleotide level. As eukaryotic DNA is organised in chromatin units, epigenetic modifications can be mediated by chromatin remodelling. Although there are a number of well-characterised chromatin remodelling factors to which we can allocate a defined molecular function, we need to understand chromatin remodelling processes as the combined effects of such factors in higher order complexes.     

Mammalian epigenomics: reprogramming the genome for development and therapy

Epigenetic modifications of DNA and chromatin are important for genome function during development and in adults. DNA and chromatin modifications have central importance for genomic imprinting and other aspects of epigenetic control of gene expression. In somatic lineages, modifications are generally stably maintained and are characteristic of different specialized tissues. The mammalian genome undergoes major reprogramming of modification patterns in germ cells and in the early embryo. Some of the factors that are involved both in maintenance and in reprogramming, such as methyltransferases, are being identified. Epigenetic reprogramming is deficient in animal cloning, which is a major explanation for the inefficiency of the cloning procedure. Deficiencies in reprogramming are likely to underlie the occurrence of epimutations and of epigenetic inheritance. Environmental factors can alter epigenetic modifications and may thus have long-lasting effects on phenotype. Epigenomics methods are being developed to catalogue genome modifications under normal and pathological conditions. Epigenetic engineering is likely to play an important role in medicine in the future.     

Epigenetic aspects of somaclonal variation in plants

Somaclonal variation is manifested as cytological abnormalities, frequent qualitative and quantitative phenotypic mutation, sequence change, and gene activation and silencing. Activation of quiescent transposable elements and retrotransposons indicate that epigenetic changes occur through the culture process. Epigenetic activation of DNA elements further suggests that epigenetic changes may also be involved in cytogenetic instability through modification of heterochromatin, and as a basis of phenotypic variation through the modulation of gene function. The observation that DNA methylation patterns are highly variable among regenerated plants and their progeny provides evidence that DNA modifications are less stable in culture than in seed-grown plants. Future research will determine the relative importance of epigenetic versus sequence or chromosome variation in conditioning somaclonal variation in plants.     

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.     

Bioinformatic tools for DNA methylation and histone modification: A survey

Epigenetic inheritance occurs due to different mechanisms such as chromatin and histone modifications, DNA methylation and processes mediated by non-coding RNAs. It leads to changes in gene expressions and the emergence of new traits in different organisms in many diseases such as cancer. Recent advances in experimental methods led to the identification of epigenetic target sites in various organisms. Computational approaches have enabled us to analyze mass data produced by these methods. Next-generation sequencing (NGS) methods have been broadly used to identify these target sites and their patterns. By using these patterns, the emergence of diseases could be prognosticated. In this study, target site prediction tools for two major epigenetic mechanisms comprising histone modification and DNA methylation are reviewed. Publicly accessible databases are reviewed as well. Some suggestions regarding the state-of-the-art methods and databases have been made, including examining patterns of epigenetic changes that are important in epigenotypes detection.     

DNA修复的表观遗传学调控

表观遗传学信息的改变是导致人类肿瘤形成的重要因素之一．基因组的稳定性经常会受到DNA损伤的威胁．然而,高度致密的染色质结构却极大地妨碍了DNA修复的进行．因此,真核生物细胞中必须有一个精确的机制来克服染色质这一天然的屏障．其中,组蛋白的共价修饰和ATP-依赖的染色质重塑通过改变染色质的结构,对DNA修复进程起着关键的调控作用．介绍了DNA修复过程中,发生在表观遗传学方面的主要调控过程,特别阐述了在DNA双链断裂损伤应答和修复过程中,组蛋白修饰和染色质重塑方面最新的研究进展,并对今后的发展方向进行了讨论．     

Retrospective and perspective of plant epigenetics in China

Epigenetics refers to the study of heritable changes in gene function that do not involve changes in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors or be part of normal developmental program. In eukaryotes, DNA wraps on a histone octamer (two copies of H2A, H2B, H3 and H4) to form nucleosome, the fundamental unit of chromatin. The structure of chromatin is subjected to a dynamic regulation through multiple epigenetic mechanisms, including DNA methylation, histone posttranslational modifications (PTMs), chromatin remodeling and noncoding RNAs. As conserved regulatory mechanisms in gene expression, epigenetic mechanisms participate in almost all the important biological processes ranging from basal development to environmental response. Importantly, all of the major epigenetic mechanisms in mammalians also occur in plants. Plant studies have provided numerous important contributions to the epigenetic research. For example, gene imprinting, a mechanism of parental allele-specific gene expression, was firstly observed in maize; evidence of paramutation, an epigenetic phenomenon that one allele acts in a single locus to induce a heritable change in the other allele, was firstly reported in maize and tomato. Moreover, some unique epigenetic mechanisms have been evolved in plants. For example, the 24-nt siRNA-involved RNA-directed DNA methylation (RdDM) pathway is plant-specific because of the involvements of two plant-specific DNA-dependent RNA polymerases, Pol IV and Pol V. A thorough study of epigenetic mechanisms is of great significance to improve crop agronomic traits and environmental adaptability. In this review, we make a brief summary of important progress achieved in plant epigenetics field in China over the past several decades and give a brief outlook on future research prospects. We focus our review on DNA methylation and histone PTMs, the two most important aspects of epigenetic mechanisms.     

Do not be scared of the genome's 5th base—Explaining phenotypic variability and evolutionary dynamics through DNA methylation analysis

Epigenetic processes have taken center stage for the investigation of many biological processes, and epigenetic modifications have shown to influence phenotype, morphology and behavioural traits such as stress resistance by affecting gene regulation and expression without altering the underlying genomic sequence. The multiple molecular layers of epigenetics synergistically construct the cell type-specific gene regulatory networks, characterized by a high degree of plasticity and redundancy to create cell-type-specific morphology and function. DNA methylation occurring on the 5′ carbon of cytosines in different genomic sequence contexts is the most studied epigenetic modification. DNA methylation has been shown to provide a molecular record of the exposure to a large variety of environmental factors, which might be persistent through the entire lifetime of an organism and even be passed onto the offspring. Animals might display altered phenotypes mediated by epigenetic modifications depending on the developmental stage or the environmental conditions as well as during evolution. Therefore, the analysis of DNA methylation patterns might allow deciphering previous exposures, explaining ecologically relevant phenotypic diversity and predicting evolutionary trajectories enabling accelerated adaption to changing environmental conditions. Despite the explanatory potential of DNA methylation integrating genetic and environmental factors to shape phenotypic variation and contribute significantly to evolutionary dynamics, studies of DNA methylation are still scarce in the field of ecology. This might be at least partly due to the complexity of DNA methylation analysis and the interpretation of the acquired data. In the current issue of Molecular Ecology Resources, Laine and colleagues (Molecular Ecology Resources, 2022) provide a detailed summary of guidelines and valuable recommendations for researchers in the field of ecology to avoid common pitfalls and perform interpretable genome-wide DNA methylation analyses.     

表观遗传标记在猪分子育种中的研究与应用前景

家畜动物的表型是由基因组、表观基因组和环境等多种因素相互影响共同作用决定的。近年来,随着遗传育种领域的迅速发展,表观遗传标记在猪分子育种中的研究受到越来越多科研人员的关注。表观遗传学是研究基因表达发生可遗传的改变而DNA序列不发生改变的一门生物学分支学科,其遗传标记主要包括DNA甲基化、组蛋白修饰、非编码RNA、印记基因等。越来越多的研究表明,表观遗传标记在猪的遗传性状中发挥着重要作用,主要通过调控与性状相关基因的表达进而达到改变生物表型的目的。然而,在当前猪分子育种领域,表观遗传标记的作用还没有得到足够的重视,影响猪重要性状的机制还没有得到深度解析,因此在实际应用中还缺乏足够的科学依据和可操作性。本文从营养、疾病、重要经济性状以及隔代遗传几个方面综述了表观遗传标记在猪分子育种中的研究现状、应用前景以及遇到的挑战,以期为表观遗传标记在猪分子育种中的应用提供较全面的理论依据。     

Experimental alteration of DNA methylation affects the phenotypic plasticity of ecologically relevant traits in <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis>

Heritable phenotypic variation in plants can be caused not only by underlying genetic differences, but also by variation in epigenetic modifications such as DNA methylation. However, we still know very little about how relevant such epigenetic variation is to the ecology and evolution of natural populations. We conducted a greenhouse experiment in which we treated a set of natural genotypes of Arabidopsis thaliana with the demethylating agent 5-azacytidine and examined the consequences of this treatment for plant traits and their phenotypic plasticity. Experimental demethylation strongly reduced the growth and fitness of plants and delayed their flowering, but the degree of this response varied significantly among genotypes. Differences in genotypes’ responses to demethylation were only weakly related to their genetic relatedness, which is consistent with the idea that natural epigenetic variation is independent of genetic variation. Demethylation also altered patterns of phenotypic plasticity, as well as the amount of phenotypic variation observed among plant individuals and genotype means. We have demonstrated that epigenetic variation can have a dramatic impact on ecologically important plant traits and their variability, as well as on the fitness of plants and their ecological interactions. Epigenetic variation may thus be an overlooked factor in the evolutionary ecology of plant populations.     

Epigenetic modulations rendering cell-to-cell variability and phenotypic metastability

Tumor cells display phenotypic plasticity and heterogeneity due to genetic and epigenetic variations which limit the predictability of therapeutic interventions.Chromatin modifications can arise stochastically but can also be a consequence of environmental influences such as the microenvironment of cancer cells.A better understanding of the impact and dynamics of epigenetic modulation at defined chromosomal sites is required to get access to the underlying mechanisms.We investigated the epigenetic modulations leading to cell-to-cell heterogeneity in a tumor cell line model.To this end,we analyzed expression variance in 80 genetically uniform cell populations having a single-copy reporter randomly integrated in the genome.Single-cell analysis showed high intraclonal heterogeneity.Epigenetic characterization revealed that expression heterogeneity was accompanied by differential histone marks whereas contribution of DNA methylation could be excluded.Strikingly,some clones revealed a highly dynamic,stochastically altered chromatin state of the transgene cassette which was accompanied with a metastable expression pattern.In contrast,other clones represented a robust chromatin state of the transgene cassette with a stable expression pattern.Together,these results elucidate locus-specific epigenetic modulation in gene expression that contributes to phenotypic heterogeneity of cells and might account for cellular plasticity.     

DNA replication components as regulators of epigenetic inheritance—lesson from fission yeast centromere

Genetic information stored in DNA is accurately copied and transferred to subsequent generations through DNA replication. This process is accomplished through the concerted actions of highly conserved DNA replication components. Epigenetic information stored in the form of histone modifications and DNA methylation, constitutes a second layer of regulatory information important for many cellular processes, such as gene expression regulation, chromatin organization, and genome stability. During DNA replication, epigenetic information must also be faithfully transmitted to subsequent generations. How this monumental task is achieved remains poorly understood. In this review, we will discuss recent advances on the role of DNA replication components in the inheritance of epigenetic marks, with a particular focus on epigenetic regulation in fission yeast. Based on these findings, we propose that specific DNA replication components function as key regulators in the replication of epigenetic information across the genome.     

Developmental consequences of imprinting of parental chromosomes by DNA methylation

Genomic imprinting by epigenetic modifications, such as DNA methylation, confers functional differences on parental chromosomes during development so that neither the male nor the female genome is by itself totipotential. We propose that maternal chromosomes are needed at the time when embryonic cells are totipotential or pluripotential, but paternal chromosomes are probably required for the proliferation of progenitor cells of differentiated tissues. Selective elimination or proliferation of embryonic cells may occur if there is an imbalance in the parental origin of some alleles. The inheritance of repressed and derepressed chromatin structures probably constitutes the initial germ-line-dependent 'imprints'. The subsequent modifications, such as changes in DNA methylation during early development, will be affected by the initial inheritance of epigenetic modifications and by the genotype-specific modifier genes. A significant number of transgene inserts are prone to reversible methylation imprinting so that paternally transmitted transgenes are undermethylated, whereas maternal transmission results in hypermethylation. Hence, allelic differences in epigenetic modifications can affect their potential for expression. The germ line evidently reverses the previously acquired epigenetic modifications before the introduction of new modifications. Errors in the reversal process could result in the transmission of epigenetic modifications to subsequent generation(s) with consequent cumulative phenotypic and grandparental effects.     

High-resolution analysis of cytosine methylation in ancient DNA

Epigenetic changes to gene expression can result in heritable phenotypic characteristics that are not encoded in the DNA itself, but rather by biochemical modifications to the DNA or associated chromatin proteins. Interposed between genes and environment, these epigenetic modifications can be influenced by environmental factors to affect phenotype for multiple generations. This raises the possibility that epigenetic states provide a substrate for natural selection, with the potential to participate in the rapid adaptation of species to changes in environment. Any direct test of this hypothesis would require the ability to measure epigenetic states over evolutionary timescales. Here we describe the first single-base resolution of cytosine methylation patterns in an ancient mammalian genome, by bisulphite allelic sequencing of loci from late Pleistocene Bison priscus remains. Retrotransposons and the differentially methylated regions of imprinted loci displayed methylation patterns identical to those derived from fresh bovine tissue, indicating that methylation patterns are preserved in the ancient DNA. Our findings establish the biochemical stability of methylated cytosines over extensive time frames, and provide the first direct evidence that cytosine methylation patterns are retained in DNA from ancient specimens. The ability to resolve cytosine methylation in ancient DNA provides a powerful means to study the role of epigenetics in evolution.     

Epigenetic regulation in plant abiotic stress responses

In eukaryotic cells, gene expression is greatly influenced by the dynamic chromatin environment. Epigenetic mechanisms, including covalent modifications to DNA and histone tails and the accessibility of chromatin, create various chromatin states for stress‐responsive gene expression that is important for adaptation to harsh environmental conditions. Recent studies have revealed that many epigenetic factors participate in abiotic stress responses, and various chromatin modifications are changed when plants are exposed to stressful environments. In this review, we summarize recent progress on the cross‐talk between abiotic stress response pathways and epigenetic regulatory pathways in plants. Our review focuses on epigenetic regulation of plant responses to extreme temperatures, drought, salinity, the stress hormone abscisic acid, nutrient limitations and ultraviolet stress, and on epigenetic mechanisms of stress memory.     

Regulatory mechanisms of mammalian imprinting

Epigenetic modifications, such as monoallelic DNA methylation, covalent histone modifications, nonhistone proteins, chromatin folding, heterochromatinization, spatial nucleus organization are reviewed with regard to establishment and maintenance of imprinting in mammals. Special attention is paid to repeated DNA sequences as intermediates of the above epigenetic modifications. A suggestion is put forward relative to importance of preimplantation development, in particular, to chromosome organization and segregation in the establishment of imprinting. Some futher directions of imprinting mechanisms are also discussed.     

Epigenetics: monoallelic expression in the immune system

Epigenetic modifications to DNA and chromatin programme important genome functions including gene expression, chromosomal architecture and stability, and the maintenance of developmental states. Recent findings further implicate epigenetic modifications in the control of allelic choice in the immune system.