Exploring and exploiting epigenetic variation in cropsThis article is one of a selection of papers from the conference “Exploiting Genome-wide Association in Oilseed Brassicas: a model for genetic improvement of major OECD crops for sustainable farming”.

Genome ◽  
2010 ◽  
Vol 53 (11) ◽  
pp. 856-868 ◽  
Author(s):  
Graham J King ◽  
Stephen Amoah ◽  
Smita Kurup
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Genetic Improvement ◽  
Developmental Stages ◽  
De Novo ◽  
Methylation Status ◽  
Intervention Strategy ◽  
Morphological Plasticity ◽  
Epigenetic Mark ◽  
Epigenetic Variation

This review addresses the mechanisms by which epigenetic variation modulates plant gene regulation and phenotype. In particular we explore the scope for harnessing such processes within the context of crop genetic improvement. We focus on the role of DNA methylation as an epigenetic mark that contributes to epiallelic diversity and modulation of gene regulation. We outline the prevalence and distribution of epigenetic marks in relation to eukaryote developmental processes, and in particular identify where this may be relevant to crop traits both in terms of specific developmental stages and in relation to physiological responses to environmental change. Recent whole genome surveys have identified specific characteristics of the distribution of DNA methylation within plant genomes. Together with greater understanding of the mode of action of different maintenance and de novo methyltransferases, this provides an opportunity to modulate DNA methylation status at specific loci as an intervention strategy in crop genetic improvement. We discuss alternative approaches that may be suitable for harnessing such induced epiallelic variation. Most of the discussion is associated with Brassica crops, which demonstrate considerable morphological plasticity, segmental chromosomal duplication, and polyploidy.

scholarly journals Infection with Human Immunodeficiency Virus Type 1 Upregulates DNA Methyltransferase, Resulting in De Novo Methylation of the Gamma Interferon (IFN-γ) Promoter and Subsequent Downregulation of IFN-γ Production

1998 ◽  
Vol 18 (9) ◽  
pp. 5166-5177 ◽  
Author(s):  
Judy A. Mikovits ◽  
Howard A. Young ◽  
Paula Vertino ◽  
Jean-Pierre J. Issa ◽  
Paula M. Pitha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Methylation Status ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Hiv 1 ◽  
De Novo Methylation

ABSTRACT The immune response to pathogens is regulated by a delicate balance of cytokines. The dysregulation of cytokine gene expression, including interleukin-12, tumor necrosis factor alpha, and gamma interferon (IFN-γ), following human retrovirus infection is well documented. One process by which such gene expression may be modulated is altered DNA methylation. In subsets of T-helper cells, the expression of IFN-γ, a cytokine important to the immune response to viral infection, is regulated in part by DNA methylation such that mRNA expression inversely correlates with the methylation status of the promoter. Of the many possible genes whose methylation status could be affected by viral infection, we examined the IFN-γ gene as a candidate. We show here that acute infection of cells with human immunodeficiency virus type 1 (HIV-1) results in (i) increased DNA methyltransferase expression and activity, (ii) an overall increase in methylation of DNA in infected cells, and (iii) the de novo methylation of a CpG dinucleotide in the IFN-γ gene promoter, resulting in the subsequent downregulation of expression of this cytokine. The introduction of an antisense methyltransferase construct into lymphoid cells resulted in markedly decreased methyltransferase expression, hypomethylation throughout the IFN-γ gene, and increased IFN-γ production, demonstrating a direct link between methyltransferase and IFN-γ gene expression. The ability of increased DNA methyltransferase activity to downregulate the expression of genes like the IFN-γ gene may be one of the mechanisms for dysfunction of T cells in HIV-1-infected individuals.

scholarly journals Modeling DNA Methylation Profiles through a Dynamic Equilibrium between Methylation and Demethylation

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1271
Author(s):  
Giulia De Riso ◽  
Damiano Francesco Giuseppe Fiorillo ◽  
Annalisa Fierro ◽  
Mariella Cuomo ◽  
Lorenzo Chiariotti ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dynamic Equilibrium ◽  
Dynamic Balance ◽  
Methylation Status ◽  
Regulatory Mechanisms ◽  
Epigenetic Mark ◽  
Transcription Start ◽  
Depth Analysis ◽  
High Depth ◽  
Methylation Profiling

DNA methylation is a heritable epigenetic mark that plays a key role in regulating gene expression. Mathematical modeling has been extensively applied to unravel the regulatory mechanisms of this process. In this study, we aimed to investigate DNA methylation by performing a high-depth analysis of particular loci, and by subsequent modeling of the experimental results. In particular, we performed an in-deep DNA methylation profiling of two genomic loci surrounding the transcription start site of the D-Aspartate Oxidase and the D-Serine Oxidase genes in different samples (n = 51). We found evidence of cell-to-cell differences in DNA methylation status. However, these cell differences were maintained between different individuals, which indeed showed very similar DNA methylation profiles. Therefore, we hypothesized that the observed pattern of DNA methylation was the result of a dynamic balance between DNA methylation and demethylation, and that this balance was identical between individuals. We hence developed a simple mathematical model to test this hypothesis. Our model reliably captured the characteristics of the experimental data, suggesting that DNA methylation and demethylation work together in determining the methylation state of a locus. Furthermore, our model suggested that the methylation status of neighboring cytosines plays an important role in this balance.

scholarly journals Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus

2020 ◽  
Vol 45 (12) ◽  
pp. 2120-2130 ◽  
Author(s):  
Gonca Bayraktar ◽  
PingAn Yuanxiang ◽  
Alessandro D. Confettura ◽  
Guilherme M. Gomes ◽  
Syed A. Raza ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Synaptic Plasticity ◽  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Memory Formation ◽  
Epigenetic Mark ◽  
Dependent Manner ◽  
Synaptic Control ◽  
Activity Dependent

Abstract DNA methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known about how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3A1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit. Interestingly, synaptic NMDARs drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3A1. This results in deficits in promoter methylation of activity-dependent genes, as well as synaptic plasticity and memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively, the data show that plasticity-relevant signals from GluN2A-containing NMDARs control activity-dependent DNA-methylation involved in memory formation.

scholarly journals DNA Methylation Changes and Its Associated Genes in Mulberry (Morus alba L.) Yu-711 Response to Drought Stress Using MethylRAD Sequencing

Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 190
Author(s):  
Michael Ackah ◽  
Liangliang Guo ◽  
Shaocong Li ◽  
Xin Jin ◽  
Charles Asakiya ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Drought Stress ◽  
Methylation Status ◽  
Enrichment Analysis ◽  
Plant Genome ◽  
Pcr Analysis ◽  
Kegg Pathways ◽  
Wide Range ◽  
And Control

Drought stress remains one of the most detrimental environmental cues affecting plant growth and survival. In this work, the DNA methylome changes in mulberry leaves under drought stress (EG) and control (CK) and their impact on gene regulation were investigated by MethylRAD sequencing. The results show 138,464 (37.37%) and 56,241 (28.81%) methylation at the CG and CWG sites (W = A or T), respectively, in the mulberry genome between drought stress and control. The distribution of the methylome was prevalent in the intergenic, exonic, intronic and downstream regions of the mulberry plant genome. In addition, we discovered 170 DMGs (129 in CG sites and 41 in CWG sites) and 581 DMS (413 in CG sites and 168 in CWG sites). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicates that phenylpropanoid biosynthesis, spliceosome, amino acid biosynthesis, carbon metabolism, RNA transport, plant hormone, signal transduction pathways, and quorum sensing play a crucial role in mulberry response to drought stress. Furthermore, the qRT-PCR analysis indicates that the selected 23 genes enriched in the KEGG pathways are differentially expressed, and 86.96% of the genes share downregulated methylation and 13.04% share upregulation methylation status, indicating the complex link between DNA methylation and gene regulation. This study serves as fundamentals in discovering the epigenomic status and the pathways that will significantly enhance mulberry breeding for adaptation to a wide range of environments.

scholarly journals Transcriptional overlap links DNA hypomethylation with DNA hypermethylation at adjacent promoters in cancer

2021 ◽  
Author(s):  
Jean S Fain ◽  
Axelle Loriot ◽  
Anna Diacofotaki ◽  
Aurelie Van Tongelen ◽  
Charles De Smet
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Tumor Development ◽  
Epigenetic Mark ◽  
Dna Hypomethylation ◽  
Dna Hypermethylation ◽  
Bioinformatics Analyses ◽  
Genomic Regions ◽  
Methylation Patterns

DNA methylation is an epigenetic mark associated with gene repression. It is now well established that tumor development involves alterations in DNA methylation patterns, which include both gains (hypermethylation) and losses (hypomethylation) of methylation marks in different genomic regions. The mechanisms underlying these two opposite, yet co-existing, alterations in tumors remain unclear. While studying the human MAGEA6/GABRA3 gene locus, we observed that DNA hypomethylation in tumor cells can lead to the activation of a long transcript (CT-GABRA3) that overlaps downstream promoters (GABRQ and GABRA3) and triggers their hypermethylation. Overlapped promoters displayed increases in H3K36me3, a histone mark known to be deposited during progression of the transcription machinery and to stimulate de novo DNA methylation. Consistent with such a processive mechanism, increases in H3K36me3 and DNA methylation were observed over the entire region covered by the CT-GABRA3 overlapping transcript. Importantly, experimental induction of CT-GABRA3 by depletion of DNMT1 DNA methyltransferase, resulted in a similar pattern of increased DNA methylation in the MAGEA6/GABRA3 locus. Bioinformatics analyses in lung cancer datasets identified other genomic loci displaying this process of coupled DNA hypo- and hypermethylation. In several of these loci, DNA hypermethylation affected tumor suppressor genes, e.g. RERG and PTPRO. Together, our work reveals that focal DNA hypomethylation in tumors can indirectly contribute to hypermethylation of nearby promoters through activation of overlapping transcription, and establishes therefore an unsuspected connection between these two opposite epigenetic alterations.

scholarly journals Global DNA methylation: role, status and genome-wide approaches to study epigenetic mark in cloned embryos

2020 ◽  
pp. 41-59
Author(s):  
Shivani Malpotra ◽  
Ahmad Hussain
Keyword(s):  
Dna Methylation ◽  
Developmental Stages ◽  
Gene Expression Pattern ◽  
Methylation Profile ◽  
Global Dna Methylation ◽  
Epigenetic Mark ◽  
Dna Methylation Profile ◽  
Low Efficiency

Somatic cell nuclear transfer (SCNT) technique has been proving its worth for more than two decades now as over 20 different species have been successfully cloned. SCNT protocol for cloning is well established but efficiency in terms of live birth rate is still low. Epigenetic abnormality following nuclear reprogramming is considered as the main culprit behind its low efficiency. DNA methylation is one of the most important epigenetic modifications that directly or indirectly regulate gene expression pattern, development and genome stability. Embryos produced through SCNT are found to express abnormal DNA methylation profile in comparison with in vivo or in vitro produced embryos. In order to improve DNA methylation profile in cloned embryos, a complete database of whole genome is required to find out specific faulty targets. Many techniques including low throughput and high throughput approach has been used to profile DNA methylation pattern in bovine embryos throughout the developmental stages. In the present review, we have compiled the overall status of global DNA methylation, the effect of aberrant DNA methylation on development and evolution in methodologies used for profiling global DNA methylome in cloned embryos.

scholarly journals The DNA Methylation Landscape of Giant Viruses

2019 ◽  
Author(s):  
Sandra Jeudy ◽  
Sofia Rigou ◽  
Jean-Marie Alempic ◽  
Jean-Michel Claverie ◽  
Chantal Abergel ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Single Molecule ◽  
Defense Mechanism ◽  
Methylation Status ◽  
Purifying Selection ◽  
Dna Methyltransferases ◽  
Epigenetic Mark ◽  
Host Defense Mechanism ◽  
Domains Of Life ◽  
Giant Viruses

AbstractDNA methylation is an important epigenetic mark that contributes to various regulations in all domains of life. Prokaryotes use it through Restriction-Modification (R-M) systems as a host-defense mechanism against viruses. The recently discovered giant viruses are widespread dsDNA viruses infecting eukaryotes with gene contents overlapping the cellular world. While they are predicted to encode DNA methyltransferases (MTases), virtually nothing is known about the DNA methylation status of their genomes. Using single-molecule real-time sequencing we studied the complete methylome of a large spectrum of families: the Marseilleviridae, the Pandoraviruses, the Molliviruses, the Mimiviridae along with their associated virophages and transpoviron, the Pithoviruses and the Cedratviruses (of which we report a new strain). Here we show that DNA methylation is widespread in giant viruses although unevenly distributed. We then identified the corresponding viral MTases, all of which are of bacterial origins and subject to intricate gene transfers between bacteria, viruses and their eukaryotic host. If some viral MTases undergo pseudogenization, most are conserved, functional and under purifying selection, suggesting that they increase the viruses’ fitness. While the Marseilleviridae, Pithoviruses and Cedratviruses DNA MTases catalyze N6-methyl-adenine modifications, some MTases of Molliviruses and Pandoraviruses unexpectedly catalyze the formation of N4-methyl-cytosine modifications. In Marseilleviridae, encoded MTases are paired with cognate restriction endonucleases (REases) forming complete R-M systems. Our data suggest that giant viruses MTases could be involved in different kind of virus-virus interactions during coinfections.

scholarly journals Methylation by multiple type I restriction modification systems avoids influencing gene regulation in uropathogenic Escherichia coli

2021 ◽  
Author(s):  
Kurosh S Mehershahi ◽  
Swaine Chen
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Dna Methylation ◽  
Gene Regulation ◽  
Detectable Effect ◽  
Epigenetic Mark ◽  
Type I ◽  
E Coli ◽  
Restriction Modification ◽  
Restriction Modification Systems

DNA methylation is a common epigenetic mark that influences transcriptional regulation, and therefore cellular phenotype, across all domains of life, extending also to bacterial virulence. Both orphan methyltransferases and those from restriction modification systems (RMSs) have been co-opted to regulate virulence epigenetically in many bacteria. However, the potential regulatory role of DNA methylation mediated by archetypal Type I systems in Escherichia coli has never been studied. We demonstrated that removal of DNA methylated mediated by three different Escherichia coli Type I RMSs in three distinct E. coli strains had no detectable effect on gene expression or growth in a screen of 1190 conditions. Additionally, deletion of the Type I RMS EcoUTI in UTI89, a prototypical cystitis strain of E. coli , which led to loss of methylation at >750 sites across the genome, had no detectable effect on virulence in a murine model of ascending urinary tract infection (UTI). Finally, introduction of two heterologous Type I RMSs into UTI89 also resulted in no detectable change in gene expression or growth phenotypes. These results stand in sharp contrast with many reports of RMSs regulating gene expression in other bacteria, leading us to propose the concept of “regulation avoidance” for these E. coli Type I RMSs. We hypothesize that regulation avoidance is a consequence of evolutionary adaptation of both the RMSs and the E. coli genome. Our results provide a clear and (currently) rare example of regulation avoidance for Type I RMSs in multiple strains of E. coli , further study of which may provide deeper insights into the evolution of gene regulation and horizontal gene transfer.

Non-canonical functions of the DNA methylome in gene regulation

2013 ◽  
Vol 451 (1) ◽  
pp. 13-23 ◽  
Author(s):  
James P. Reddington ◽  
Sari Pennings ◽  
Richard R. Meehan
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Transcriptional Regulation ◽  
Polycomb Group ◽  
Epigenetic Mark ◽  
Regulation Of Transcription ◽  
Gene Promoters ◽  
Dna Modification ◽  
Dna Methylome ◽  
Genomic Regions

Methylation of the cytosine base in DNA, DNA methylation, is an essential epigenetic mark in mammals that contributes to the regulation of transcription. Several advances have been made in this area in recent years, leading to a leap forward in our understanding of how this pathway contributes to gene regulation during embryonic development, and the functional consequences of its perturbation in human disease. Critical to these advances is a comprehension of the genomic distribution of modified cytosine bases in unprecedented detail, drawing attention to genomic regions beyond gene promoters. In addition, we have a more complete understanding of the multifactorial manner by which DNA methylation influences gene regulation at the molecular level, and which genes rely directly on the DNA methylome for their normal transcriptional regulation. It is becoming apparent that a major role of DNA modification is to act as a relatively stable, and mitotically heritable, template that contributes to the establishment and maintenance of chromatin states. In this regard, interplay is emerging between DNA methylation and the PcG (Polycomb group) proteins, which act as evolutionarily conserved mediators of cell identity. In the present paper we review these aspects of DNA methylation, and discuss how a multifunctional view of DNA modification as an integral part of chromatin organization is influencing our understanding of this epigenetic mark's contribution to transcriptional regulation.

scholarly journals DNA Demethylation Pathways: Recent Insights

2013 ◽  
Vol 5 ◽  
pp. GEG.S12143 ◽  
Author(s):  
Cong-jun Li
Keyword(s):  
Dna Methylation ◽  
Mammalian Cells ◽  
De Novo ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Sequencing Technologies ◽  
Active Dna Demethylation ◽  
Mammalian Genomes ◽  
Genome Context

DNA methylation is a major epigenetic regulatory mechanism for gene expression and cell differentiation. Until recently, it was still unclear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether or not active demethylating activity is involved. Even the role of molecules and the mechanisms underlying the processes of active demethylation itself is blurred. Emerging sequencing technologies have led to recent insights into the dynamic distribution of DNA methylation during development and the role of this epigenetic mark within a distinct genome context, such as the promoters, exons, or imprinted control regions. This review summarizes recent insights on the dynamic nature of DNA methylation and demethylation, as well as the mechanisms regulating active DNA demethylation in mammalian cells, which have been fundamental research interests in the field of epigenomics.

Sign in / Sign up

Export Citation Format

Share Document