scholarly journals Induced Methylation in Plants as a Crop Improvement Tool: Progress and Perspectives

Agronomy ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1484
Author(s):  
Clémentine Mercé ◽  
Philipp E. Bayer ◽  
Cassandria Tay Fernandez ◽  
Jacqueline Batley ◽  
David Edwards
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epigenetic Modification ◽  
Crop Improvement ◽  
Regulation Of Gene Expression ◽  
Gene Promoters ◽  
Control Of Gene Expression ◽  
Underlying Mechanisms ◽  
Successive Generations ◽  
Methylation Patterns

The methylation of gene promoters is an epigenetic process that can have a major impact on plant phenotypes through its control of gene expression. This phenomenon can be observed as a response to stress, such as drought, cold/heat stress or pathogen infection. The transgenerational heritability of DNA methylation marks could enable breeders to fix beneficial methylation patterns in crops over successive generations. These properties of DNA methylation, its impact on the phenotype and its heritability, could be used to support the accelerated breeding of improved crop varieties. Induced DNA methylation has the potential to complement the existing plant breeding process, supporting the introduction of desirable characteristics in crops within a single generation that persist in its progeny. Therefore, it is important to understand the underlying mechanisms involved in the regulation of gene expression through DNA methylation and to develop methods for precisely modulating methylation patterns for crop improvement. Here we describe the currently available epigenetic editing tools and their advantages and limitations in the domain of crop breeding. Finally, we discuss the biological and legislative limitations currently restricting the development of epigenetic modification as a crop improvement tool.

scholarly journals DNA Methylation, Epigenetics, and Evolution in Vertebrates: Facts and Challenges

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Annalisa Varriale
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Environmental Influence ◽  
Epigenetic Modification ◽  
Regulation Of Gene Expression ◽  
Entire Genome ◽  
Phenotypic Differences ◽  
Methylation Patterns ◽  
And Control

DNA methylation is a key epigenetic modification in the vertebrate genomes known to be involved in biological processes such as regulation of gene expression, DNA structure and control of transposable elements. Despite increasing knowledge about DNA methylation, we still lack a complete understanding of its specific functions and correlation with environment and gene expression in diverse organisms. To understand how global DNA methylation levels changed under environmental influence during vertebrate evolution, we analyzed its distribution pattern along the whole genome in mammals, reptiles and fishes showing that it is correlated with temperature, independently on phylogenetic inheritance. Other studies in mammals and plants have evidenced that environmental stimuli can promote epigenetic changes that, in turn, might generate localized changes in DNA sequence resulting in phenotypic effects. All these observations suggest that environment can affect the epigenome of vertebrates by generating hugely different methylation patterns that could, possibly, reflect in phenotypic differences. We are at the first steps towards the understanding of mechanisms that underlie the role of environment in molding the entire genome over evolutionary times. The next challenge will be to map similarities and differences of DNA methylation in vertebrates and to associate them with environmental adaptation and evolution.

scholarly journals DNA Methylation of Enhancer Elements in Myeloid Neoplasms: Think Outside the Promoters?

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1424 ◽  
Author(s):  
Ordoñez ◽  
Martínez-Calle ◽  
Agirre ◽  
Prosper
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epigenetic Modification ◽  
Myeloproliferative Neoplasms ◽  
Regulation Of Gene Expression ◽  
Fine Tuning ◽  
Specific Gene ◽  
Gene Promoters ◽  
Regulatory Regions ◽  
Genome Wide

Gene regulation through DNA methylation is a well described phenomenon that has a prominent role in physiological and pathological cell-states. This epigenetic modification is usually grouped in regions denominated CpG islands, which frequently co-localize with gene promoters, silencing the transcription of those genes. Recent genome-wide DNA methylation studies have challenged this paradigm, demonstrating that DNA methylation of regulatory regions outside promoters is able to influence cell-type specific gene expression programs under physiologic or pathologic conditions. Coupling genome-wide DNA methylation assays with histone mark annotation has allowed for the identification of specific epigenomic changes that affect enhancer regulatory regions, revealing an additional layer of complexity to the epigenetic regulation of gene expression. In this review, we summarize the novel evidence for the molecular and biological regulation of DNA methylation in enhancer regions and the dynamism of these changes contributing to the fine-tuning of gene expression. We also analyze the contribution of enhancer DNA methylation on the expression of relevant genes in acute myeloid leukemia and chronic myeloproliferative neoplasms. The characterization of the aberrant enhancer DNA methylation provides not only a novel pathogenic mechanism for different tumors but also highlights novel potential therapeutic targets for myeloid derived neoplasms.

Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jessilyn Dunn ◽  
Haiwei Qiu ◽  
Soyeon Kim ◽  
Daudi Jjingo ◽  
Ryan Hoffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Western Diet ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

scholarly journals TET2 coactivates gene expression through demethylation of enhancers

2018 ◽  
Vol 4 (11) ◽  
pp. eaau6986 ◽  
Author(s):  
Lu Wang ◽  
Patrick A. Ozark ◽  
Edwin R. Smith ◽  
Zibo Zhao ◽  
Stacy A. Marshall ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Regulation Of Gene Expression ◽  
Estrogen Receptor Α ◽  
Dna Demethylation ◽  
Estrogen Response ◽  
Dna Base ◽  
Modified Dna ◽  
Global Increase ◽  
Methylation Patterns

The tet methylcytosine dioxygenase 2 (TET2) enzyme catalyzes the conversion of the modified DNA base 5-methylcytosine to 5-hydroxymethylcytosine. TET2 is frequently mutated or dysregulated in multiple human cancers, and loss of TET2 is associated with changes in DNA methylation patterns. Here, using newly developed TET2-specific antibodies and the estrogen response as a model system for studying the regulation of gene expression, we demonstrate that endogenous TET2 occupies active enhancers and facilitates the proper recruitment of estrogen receptor α (ERα). Knockout of TET2 by CRISPR-CAS9 leads to a global increase of DNA methylation at enhancers, resulting in attenuation of the estrogen response. We further identified a positive feedback loop between TET2 and ERα, which further requires MLL3 COMPASS at these enhancers. Together, this study reveals an epigenetic axis coordinating a transcriptional program through enhancer activation via DNA demethylation.

Regulation of gene expression by DNA methylation with cytotoxic T lymphocytes evaluation in consensus molecular subtypes of colorectal cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 25-25
Author(s):  
Yuanyuan Shen ◽  
Justin Hummel ◽  
Isabel Cristina Trindade ◽  
Christos Papageorgiou ◽  
Chi-Ren Shyu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Dna Methylation ◽  
Molecular Subtypes ◽  
Epigenetic Modification ◽  
Pearson Correlation ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
The Cancer Genome Atlas ◽  
Highly Correlated

25 Background: Low cytotoxic T lymphocyte (CTLs) infiltration in colorectal cancer (CRC) tumors is a challenge to treatment with immune checkpoint inhibitors. Consensus molecular subtypes (CMS) classify patients based on tumor attributes, and CMS1 patients include the majority of patients with high CTL infiltration and “inflamed” tumors. Epigenetic modification plays a critical role in gene expression and therapy resistance. Therefore, in this study we compared DNA methylation, gene expression, and CTL infiltration of CMS1 patients to other CMS groups to determine targets for improving immunotherapy in CRC. Methods: RNA-seq (n = 511) and DNA methylation (n = 316) from The Cancer Genome Atlas databases were used to determine gene expression and methylation profiles based on CMSs. CMS1 was used as a reference and compared to other subtypes (CMS2-4). Microenvironment Cell Populations- counter (MCPcounter) was used to determine tumor CTL infiltration. Genes with significantly different expression (p < 0.01, LogFC≥|1.5|) and difference of mean methylation β value ≥|0.25| were integrated for Pearson correlation coefficient analysis with MCPcounter score (r > |0.7|). Results: Comparing CMS1 and CMS2, ARHGAP9, TBX21, and LAG3 were differentially methylated and correlated with CTL scores. ARHGAP9 and TBX21 were decreased and hypomethylated in CMS2. Comparing CMS1 and CMS3, ARHGAP9, TBX21, FMNL1, HLA-DPB1, and STX11 were downregulated in CMS3 and highly correlated with CTL scores. ARHGAP9, FMNL1, HLA-DPB1, and STX11 were hypomethylated in CMS3 and TBX21 was methylated in both, but had a higher methylation ratio in CMS1. Comparing CMS1 and CMS4, TBX21 was the only gene downregulated, hypomethylated, and highly correlated with CTL scores in CMS4 patients. Conclusions: We found six genes differentially expressed, differentially methylated, and highly correlated with CTL infiltration when comparing CMS1 to other CMS groups. Specifically, TBX21 was the only gene highly correlated with CTL scores with differential gene expression and methylation in CMS2-4 when compared to CMS1. Thus, T-bet may be a critical regulator of T cell responses in CRC.

scholarly journals Non-coding RNAs and DNA methylation in plants

2014 ◽  
Vol 1 (2) ◽  
pp. 219-229 ◽  
Author(s):  
Yuanyuan Zhao ◽  
Xuemei Chen
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epigenetic Modification ◽  
Genome Integrity ◽  
Non Coding Rnas ◽  
Methylation Patterns

Abstract Cytosine DNA methylation is an epigenetic modification in eukaryotes that maintains genome integrity and regulates gene expression. The DNA methylation patterns in plants are more complex than those in animals, and plants and animals have common as well as distinct pathways in regulating DNA methylation. Recent studies involving genetic, molecular, biochemical and genomic approaches have greatly expanded our knowledge of DNA methylation in plants. The roles of many proteins as well as non-coding RNAs in DNA methylation have been uncovered.

scholarly journals Tet1 and Tet2 Protect DNA Methylation Canyons against Hypermethylation

2015 ◽  
Vol 36 (3) ◽  
pp. 452-461 ◽  
Author(s):  
Laura Wiehle ◽  
Günter Raddatz ◽  
Tanja Musch ◽  
Meelad M. Dawlaty ◽  
Rudolf Jaenisch ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Fate ◽  
Epigenetic Modification ◽  
Regulation Of Gene Expression ◽  
Mechanistic Explanation ◽  
Dna Demethylation ◽  
Double Knockout ◽  
Developmental Defects ◽  
Active Dna Demethylation ◽  
Underlying Mechanisms

DNA methylation is a dynamic epigenetic modification with an important role in cell fate specification and reprogramming. The Ten eleven translocation (Tet) family of enzymes converts 5-methylcytosine to 5-hydroxymethylcytosine, which promotes passive DNA demethylation and functions as an intermediate in an active DNA demethylation process. Tet1/Tet2 double-knockout mice are characterized by developmental defects and epigenetic instability, suggesting a requirement for Tet-mediated DNA demethylation for the proper regulation of gene expression during differentiation. Here, we used whole-genome bisulfite and transcriptome sequencing to characterize the underlying mechanisms. Our results uncover the hypermethylation of DNA methylation canyons as the genomic key feature of Tet1/Tet2 double-knockout mouse embryonic fibroblasts. Canyon hypermethylation coincided with disturbed regulation of associated genes, suggesting a mechanistic explanation for the observed Tet-dependent differentiation defects. Based on these results, we propose an important regulatory role of Tet-dependent DNA demethylation for the maintenance of DNA methylation canyons, which prevents invasive DNA methylation and allows functional regulation of canyon-associated genes.

scholarly journals Interaction between early in ovo stimulation of the gut microbiota and chicken host – splenic changes in gene expression and methylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
A. Dunislawska ◽  
A. Slawinska ◽  
M. Gryzinska ◽  
M. Siwek
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Regulation Of Gene Expression ◽  
Gene Promoters ◽  
Gene Methylation ◽  
In Ovo ◽  
Bioactive Substances ◽  
Global Methylation ◽  
D 12 ◽  
Methylation Patterns

Abstract Background Epigenetic regulation of the gene expression results from interaction between the external environment and transcription of the genetic information encoded in DNA. Methylated CpG regions within the gene promoters lead to silencing of the gene expression in most cases. Factors contributing to epigenetic regulation include intestinal microbiota, which in chicken can be potently modified by in ovo stimulation. The main aim of this study was to determine global and specific methylation patterns of the spleen under the influence of host-microbiome interaction. Results Fertilized eggs of two genotypes: Ross 308 and Green-legged Partridgelike were in ovo stimulated on d 12 of incubation. The injected compounds were as follows: probiotic – Lactococcus lactis subsp. cremoris IBB477, prebiotic – galactooligosaccharides, and synbiotic – combination of both. Chickens were sacrificed on d 42 post-hatching. Spleen was collected, RNA and DNA were isolated and intended to gene expression, gene methylation and global methylation analysis. We have proved that negative regulation of gene expression after administration of bioactive substances in ovo might have epigenetic character. Epigenetic changes depend on the genotype and the substance administered in ovo. Conclusion Epigenetic nature of microbial reprogramming in poultry and extension of issues related to host-microbiome interaction is a new direction of this research.

scholarly journals Epigenetic regulations through DNA methylation and hydroxymethylation: clues for early pregnancy in decidualization

2014 ◽  
Vol 5 (2) ◽  
pp. 95-107 ◽  
Author(s):  
Fei Gao ◽  
Sanjoy K. Das
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Fate ◽  
High Throughput Sequencing ◽  
Gene Expression Regulation ◽  
Epigenetic Modification ◽  
Regulation Of Gene Expression ◽  
Reproductive Organ ◽  
Epigenetic Changes ◽  
Dynamic Regulation

AbstractDNA methylation at cytosines is an important epigenetic modification that participates in gene expression regulation without changing the original DNA sequence. With the rapid progress of high-throughput sequencing techniques, whole-genome distribution of methylated cytosines and their regulatory mechanism have been revealed gradually. This has allowed the uncovering of the critical roles played by DNA methylation in the maintenance of cell pluripotency, determination of cell fate during development, and in diverse diseases. Recently, rediscovery of 5-hydroxymethylcytosine, and other types of modification on DNA, have uncovered more dynamic aspects of cell methylome regulation. The interaction of DNA methylation and other epigenetic changes remodel the chromatin structure and determine the state of gene transcription, not only permanently, but also transiently under certain stimuli. The uterus is a reproductive organ that experiences dramatic hormone stimulated changes during the estrous cycle and pregnancy, and thus provides us with a unique model for studying the dynamic regulation of epigenetic modifications. In this article, we review the current findings on the roles of genomic DNA methylation and hydroxymethylation in the regulation of gene expression, and discuss the progress of studies for these epigenetic changes in the uterus during implantation and decidualization.

scholarly journals Changes in Methylation Patterns of Kiss1 and Kiss1r Gene Promoters across Puberty

2013 ◽  
Vol 5 ◽  
pp. GEG.S12897 ◽  
Author(s):  
Amanda K. Wyatt ◽  
Monika Zavodna ◽  
Jean L. Viljoen ◽  
Jo-Ann L. Stanton ◽  
Neil J. Gemmell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Female Rats ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Loss Of Function ◽  
Control Of Gene Expression ◽  
Environmental Signals ◽  
Before And After ◽  
Methylation Patterns ◽  
Pubertal Transition

The initiation of mammalian puberty is underpinned by an increase in Kisspeptin (Kiss1) signaling via its receptor (Kiss1r/GPR54) on gonadotropin-releasing hormone (GnRH) neurons. Animals and humans with loss-of-function mutations in Kiss1 or Kiss1r fail to go through puberty. The timing of puberty is dependent on environmental factors, and malleability in puberty timing suggests a mechanism that can translate environmental signals into patterns of Kiss1/Kiss1r gene expression. Epigenetics is a powerful mechanism that can control gene expression in an environment-dependent manner. We investigated whether epigenetic DNA methylation is associated with gene expression changes at puberty. We used bisulfite-PCR-pyrosequencing to define the methylation in the promoters of Kiss1 and Kiss1r before and after puberty in female rats. Both Kiss1 and Kiss1r showed highly significant puberty-specific differential promoter methylation patterns. By identifying key differentially methylated residues associated with puberty, these findings will be important for further studies investigating the control of gene expression across the pubertal transition.

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