DNA methylation versus gene expression

Development ◽  
1984 ◽  
Vol 83 (Supplement) ◽  
pp. 31-40
Author(s):  
Adrian P. Bird
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Division ◽  
Methylation Pattern ◽  
Current Evidence ◽  
Evolutionary Perspective ◽  
Cell Type ◽  
Versus Gene ◽  
Daughter Cells ◽  
The Relationship

Vertebrate DNA is methylated at a high proportion of cytosine residues in the sequence CpG, and it has been suggested that the distribution of methylated and non-methylated CpGs in a given cell type influences the pattern of gene expression in those cells. Since a DNA methylation pattern is normally transmitted faithfully to daughter cells via cell division, this idea suggests an origin for stable, clonally inherited patterns of gene expression. This article discusses some of the current evidence for a relationship between DNA methylation and gene expression. Although the evidence is incomplete, it appears already that the relationship is variable: transcription of some genes is repressed by the presence of 5-methylcytosine at certain CpGs, and may be controlled by methylation, while transcription of other genes is indifferent to methylation. In attempting to explain this variability it is helpful to adopt an evolutionary perspective.

scholarly journals Identification of blood autosomal cis-expression quantitative trait methylation (cis-eQTMs) in children

2020 ◽  
Author(s):  
Carlos Ruiz-Arenas ◽  
Carles Hernandez-Ferrer ◽  
Marta Vives-Usano ◽  
Sergi Marí ◽  
Inés Quintela ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Quantitative Trait ◽  
Association Studies ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Biological Interpretation ◽  
Cell Type Specific ◽  
Using Data ◽  
The Relationship

AbstractBackgroundThe identification of expression quantitative trait methylation (eQTMs), defined as correlations between gene expression and DNA methylation levels, might help the biological interpretation of epigenome-wide association studies (EWAS). We aimed to identify autosomal cis-eQTMs in child blood, using data from 832 children of the Human Early Life Exposome (HELIX) project.MethodsBlood DNA methylation and gene expression were measured with the Illumina 450K and the Affymetrix HTA v2 arrays, respectively. The relationship between methylation levels and expression of nearby genes (transcription start site (TSS) within a window of 1 Mb) was assessed by fitting 13.6 M linear regressions adjusting for sex, age, and cohort.ResultsWe identified 63,831 autosomal cis-eQTMs, representing 35,228 unique CpGs and 11,071 unique transcript clusters (TCs, genes). 74.3% of these cis-eQTMs were located at <250 kb, 60.0% showed an inverse relationship and 23.9% had at least one genetic variant associated with the methylation and expression levels. They were enriched for active blood regulatory regions. Adjusting for cellular composition decreased the number of cis-eQTMs to 37.7%, suggesting that some of them were cell type-specific. The overlap of child blood cis-eQTMs with those described in adults was small, and child and adult shared cis-eQTMs tended to be proximal to the TSS, enriched for genetic variants and with lower cell type specificity. Only half of the cis-eQTMs could be captured through annotation to the closest gene.ConclusionsThis catalogue of blood autosomal cis-eQTMs in children can help the biological interpretation of EWAS findings, and is publicly available at https://helixomics.isglobal.org/.

scholarly journals DNA methylation and gene expression integration in cardiovascular disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Guillermo Palou-Márquez ◽  
Isaac Subirana ◽  
Lara Nonell ◽  
Alba Fernández-Sanlés ◽  
Roberto Elosua
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cardiovascular Diseases ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Risk Function ◽  
Predictive Biomarkers ◽  
Independent Study ◽  
Cell Type

Abstract Background The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1.0 ST Array; Affymetrix). Using the MOFA2 R package, we integrated these data to identify biomarkers related to the risk of presenting a cardiovascular event. Results Four independent latent factors (9, 19, 21—only in women—and 27), driven by DNA methylation, were associated with cardiovascular disease independently of classical risk factors and cell-type counts. In a sensitivity analysis, we also identified factor 21 as associated with CVD in women. Factors 9, 21 and 27 were also associated with coronary heart disease risk. Moreover, in a replication effort in an independent study three of the genes included in factor 27 were also present in a factor identified to be associated with myocardial infarction (CDC42BPB, MAN2A2 and RPTOR). Factor 9 was related to age and cell-type proportions; factor 19 was related to age and B cells count; factor 21 pointed to human immunodeficiency virus infection-related pathways and inflammation; and factor 27 was related to lifestyle factors such as alcohol consumption, smoking and body mass index. Inclusion of factor 21 (only in women) improved the discriminative and reclassification capacity of the Framingham classical risk function and factor 27 improved its discrimination. Conclusions Unsupervised multi-omics data integration methods have the potential to provide insights into the pathogenesis of cardiovascular diseases. We identified four independent factors (one only in women) pointing to inflammation, endothelium homeostasis, visceral fat, cardiac remodeling and lifestyles as key players in the determination of cardiovascular risk. Moreover, two of these factors improved the predictive capacity of a classical risk function.

scholarly journals Leveraging DNA-Methylation Quantitative-Trait Loci to Characterize the Relationship between Methylomic Variation, Gene Expression, and Complex Traits

2018 ◽  
Vol 103 (5) ◽  
pp. 654-665 ◽  
Author(s):  
Eilis Hannon ◽  
Tyler J. Gorrie-Stone ◽  
Melissa C. Smart ◽  
Joe Burrage ◽  
Amanda Hughes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Complex Traits ◽  
Trait Loci ◽  
The Relationship ◽  
Methylation Quantitative Trait Loci

scholarly journals Leveraging DNA methylation quantitative trait loci to characterize the relationship between methylomic variation, gene expression and complex traits

2018 ◽  
Author(s):  
Eilis Hannon ◽  
Tyler J Gorrie-Stone ◽  
Melissa C Smart ◽  
Joe Burrage ◽  
Amanda Hughes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Genetic Variation ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Complex Traits ◽  
Common Genetic Variation ◽  
Online Data ◽  
The Relationship ◽  
Methylation Quantitative Trait Loci

ABSTRACTCharacterizing the complex relationship between genetic, epigenetic and transcriptomic variation has the potential to increase understanding about the mechanisms underpinning health and disease phenotypes. In this study, we describe the most comprehensive analysis of common genetic variation on DNA methylation (DNAm) to date, using the Illumina EPIC array to profile samples from the UK Household Longitudinal study. We identified 12,689,548 significant DNA methylation quantitative trait loci (mQTL) associations (P < 6.52x10-14) occurring between 2,907,234 genetic variants and 93,268 DNAm sites, including a large number not identified using previous DNAm-profiling methods. We demonstrate the utility of these data for interpreting the functional consequences of common genetic variation associated with > 60 human traits, using Summary data–based Mendelian Randomization (SMR) to identify 1,662 pleiotropic associations between 36 complex traits and 1,246 DNAm sites. We also use SMR to characterize the relationship between DNAm and gene expression, identifying 6,798 pleiotropic associations between 5,420 DNAm sites and the transcription of 1,702 genes. Our mQTL database and SMR results are available via a searchable online database (http://www.epigenomicslab.com/online-data-resources/) as a resource to the research community.

scholarly journals Title Page Title: The role of DNA methylation in the accumulation of iridoid glycosides in Rehmannia glutinosa

2021 ◽  
Author(s):  
Tianyu Dong ◽  
Xiaoyan Wei ◽  
Qianting Qi ◽  
Peilei Chen ◽  
Yanqing Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Secondary Metabolites ◽  
Iridoid Glycosides ◽  
Methylation Status ◽  
Plant Secondary Metabolites ◽  
Dna Demethylation ◽  
Terpene Biosynthesis ◽  
The Relationship

Abstract Background: Epigenetic regulation plays a significant role in the accumulation of plant secondary metabolites. The terpenoids are the most abundant in the secondary metabolites of plants, iridoid glycosides belong to monoterpenoids which is one of the main medicinal components of R.glutinosa. At present, study on iridoid glycosides mainly focuses on its pharmacology, accumulation and distribution, while the mechanism of its biosynthesis and the relationship between DNA methylation and plant terpene biosynthesis are seldom reports. Results: The research showed that the expression of DXS, DXR, 10HGO, G10H, GPPS and accumulation of iridoid glycosides increased at first and then decreased with the maturity of R.glutinosa, and under different concentrations of 5-azaC, the expression of DXS, DXR, 10HGO, G10H, GPPS and the accumulation of total iridoid glycosides were promoted, the promotion effect of low concentration (15μM-50μM) was more significant, the content of genomic DNA 5mC decreased significantly, the DNA methylation status of R.glutinosa genomes was also changed. DNA demethylation promoted gene expression and increased the accumulation of iridoid glycosides, but excessive demethylation inhibited gene expression and decreased the accumulation of iridoid glycosides. Conclusion: The analysis of DNA methylation, gene expression, and accumulation of iridoid glycoside provides insights into accumulation of terpenoids in R.glutinosa and lays a foundation for future studies on the effects of epigenetics on the synthesis of secondary metabolites.

scholarly journals Methylation pattern polymorphism of cyp19a in Nile tilapia and hybrids

2018 ◽  
Vol 13 (1) ◽  
pp. 327-334 ◽  
Author(s):  
Xiaowu Chen ◽  
Yonghua Zhao ◽  
Yudong He ◽  
Jinliang Zhao
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Methylation Pattern ◽  
Male Ratio ◽  
Sex Development ◽  
Pattern Polymorphism ◽  
Fish Hybrids

AbstractSkewed sex development is prevalent in fish hybrids. However, the histological observation and molecular mechanisms remain elusive. In this study, we showed that the interspecific hybrids of the two fish species, Oreochromis niloticus and Oreochromis aureus, had a male ratio of 98.02%. Microscopic examination revealed that the gonads of both male and female hybrids were developmentally retarded. Compared with the ovaries, the testes of both O. niloticus and hybrids showed higher DNA methylation level in two selected regions in the promoter of cyp19a, the gonadal aromatase gene that converts androgens into estrogens, cyp19a showed higher level gene expression in the ovary than in the testis in both O. niloticus and hybrid tilapia. Methylation and gene expression level of cyp19a were negative correlation between the testis and ovary. Gene transcription was suppressed by the methylation of the cyp19a promoter in vitro. While there is no obvious difference of the methylation level in testis or ovary between O. niloticus and hybrids. Thus, the DNA methylation of the promoter of cyp19a may be an essential component of the sex maintenance, but not a determinant of high male ratio and developmental retardation of gonads in tilapia hybrids.

scholarly journals Smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic traits

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Silvana C. E. Maas ◽  
Michelle M. J. Mens ◽  
Brigitte Kühnel ◽  
Joyce B. J. van Meurs ◽  
André G. Uitterlinden ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Association Study ◽  
Multiple Testing ◽  
Molecular Mechanisms ◽  
Mediation Effect ◽  
Rotterdam Study ◽  
Versus Gene ◽  
Metabolic Trait ◽  
Metabolic Traits

Abstract Background Tobacco smoking is a well-known modifiable risk factor for many chronic diseases, including cardiovascular disease (CVD). One of the proposed underlying mechanism linking smoking to disease is via epigenetic modifications, which could affect the expression of disease-associated genes. Here, we conducted a three-way association study to identify the relationship between smoking-related changes in DNA methylation and gene expression and their associations with cardio-metabolic traits. Results We selected 2549 CpG sites and 443 gene expression probes associated with current versus never smokers, from the largest epigenome-wide association study and transcriptome-wide association study to date. We examined three-way associations, including CpG versus gene expression, cardio-metabolic trait versus CpG, and cardio-metabolic trait versus gene expression, in the Rotterdam study. Subsequently, we replicated our findings in The Cooperative Health Research in the Region of Augsburg (KORA) study. After correction for multiple testing, we identified both cis- and trans-expression quantitative trait methylation (eQTM) associations in blood. Specifically, we found 1224 smoking-related CpGs associated with at least one of the 443 gene expression probes, and 200 smoking-related gene expression probes to be associated with at least one of the 2549 CpGs. Out of these, 109 CpGs and 27 genes were associated with at least one cardio-metabolic trait in the Rotterdam Study. We were able to replicate the associations with cardio-metabolic traits of 26 CpGs and 19 genes in the KORA study. Furthermore, we identified a three-way association of triglycerides with two CpGs and two genes (GZMA; CLDND1), and BMI with six CpGs and two genes (PID1; LRRN3). Finally, our results revealed the mediation effect of cg03636183 (F2RL3), cg06096336 (PSMD1), cg13708645 (KDM2B), and cg17287155 (AHRR) within the association between smoking and LRRN3 expression. Conclusions Our study indicates that smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic risk factors. These findings may provide additional insights into the molecular mechanisms linking smoking to the development of CVD.

scholarly journals Compartment-specific transcriptomics of ozone-exposed murine lungs reveals sex and cell type-associated perturbations relevant to mucoinflammatory lung diseases

2020 ◽  
Author(s):  
Ishita Choudhary ◽  
Thao Vo ◽  
Kshitiz Paudel ◽  
Sonika Patial ◽  
Yogesh Saini
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Cell Division ◽  
Mucous Cell ◽  
Ozone Exposure ◽  
Specific Gene ◽  
Cell Type ◽  
Distinct Cell Type ◽  
Airway Injury ◽  
Immunohistochemical Analyses

Ozone is known to cause lung injury and resident cells of the respiratory tract, i.e., epithelial cells and macrophages, respond to inhaled ozone in a variety of ways that affect their survival, morphology, and functioning. However, a complete understanding of the sex-associated and the cell type-specific gene expression changes in response to ozone exposure is still limited. Through transcriptomics, we aimed to analyze gene expression alterations and associated enrichment of biological pathways enrichment in three distinct cell type-enriched compartments of ozone-exposed murine lungs. We sub-chronically exposed adult males and females to 0.8ppm ozone or filtered air. RNA-Seq was performed on airway epithelium-enriched airways, parenchyma, and purified airspace macrophages. Differential gene expression and biological pathway analyses were performed and supported by cellular and immunohistochemical analyses. While a majority of differentially expressed genes (DEGs) in ozone-exposed versus air-exposed groups were common between both sexes, sex-specific DEGs were also identified in all the three tissue compartments. As compared to ozone-exposed males, ozone-exposed females had significant alterations in gene expression in three compartments. Pathways relevant to cell division and DNA repair were enriched in the ozone-exposed airways indicating ozone-induced airway injury and repair which was further supported by immunohistochemical analyses. In addition to cell division and DNA repair pathways, inflammatory pathways were also enriched within the parenchyma supporting contribution by both epithelial and immune cells. Finally, immune response and cytokine-cytokine receptor interactions were enriched in macrophages, indicating ozone-induced macrophage activation. Lastly, our analyses also revealed ozone-induced upregulation of mucoinflammation- and mucous cell metaplasia-associated pathways.

scholarly journals Impact of Transposable Elements on Methylation and Gene Expression across Natural Accessions of Brachypodium distachyon

2020 ◽  
Vol 12 (11) ◽  
pp. 1994-2001 ◽  
Author(s):  
Michele Wyler ◽  
Christoph Stritt ◽  
Jean-Claude Walser ◽  
Célia Baroux ◽  
Anne C Roulin
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transposable Elements ◽  
Brachypodium Distachyon ◽  
Large Fraction ◽  
Expression Patterns ◽  
Specific Gene ◽  
Differential Gene ◽  
The Relationship ◽  
Silent State

Abstract Transposable elements (TEs) constitute a large fraction of plant genomes and are mostly present in a transcriptionally silent state through repressive epigenetic modifications, such as DNA methylation. TE silencing is believed to influence the regulation of adjacent genes, possibly as DNA methylation spreads away from the TE. Whether this is a general principle or a context-dependent phenomenon is still under debate, pressing for studying the relationship between TEs, DNA methylation, and nearby gene expression in additional plant species. Here, we used the grass Brachypodium distachyon as a model and produced DNA methylation and transcriptome profiles for 11 natural accessions. In contrast to what is observed in Arabidopsis thaliana, we found that TEs have a limited impact on methylation spreading and that only few TE families are associated with a low expression of their adjacent genes. Interestingly, we found that a subset of TE insertion polymorphisms is associated with differential gene expression across accessions. Thus, although not having a global impact on gene expression, distinct TE insertions may contribute to specific gene expression patterns in B. distachyon.

scholarly journals CRISPR-mediated modification of DNA methylation pattern in the new era of cancer therapy

Epigenomics ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 1845-1859
Author(s):  
Faezeh Maroufi ◽  
Amirhosein Maali ◽  
Meghdad Abdollahpour-Alitappeh ◽  
Mohammad Hossein Ahmadi ◽  
Mehdi Azad
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cancer Progression ◽  
Methylation Pattern ◽  
Epigenetic Therapy ◽  
Special Importance ◽  
New Era ◽  
Major Mechanism ◽  
Aberrant Dna Methylation ◽  
Normal Status

In the last 2 decades, a wide variety of studies have been conducted on epigenetics and its role in various cancers. A major mechanism of epigenetic regulation is DNA methylation, including aberrant DNA methylation variations such as hypermethylation and hypomethylation in the promoters of critical genes, which are commonly detected in tumors and mark the early stages of cancer development. Therefore, epigenetic therapy has been of special importance in the last decade for cancer treatment. In epigenetic therapy, all efforts are made to modulate gene expression to the normal status. Importantly, recent studies have shown that epigenetic therapy is focusing on the new gene editing technology, CRISPR-Cas9. This tool was found to be able to effectively modulate gene expression and alter almost any sequence in the genome of cells, resulting in events such as a change in acetylation, methylation, or histone modifications. Of note, the CRISPR-Cas9 system can be used for the treatment of cancers caused by epigenetic alterations. The CRISPR-Cas9 system has greater advantages than other available methods, including potent activity, easy design and high velocity as well as the ability to target any DNA or RNA site. In this review, we described epigenetic modulators, which can be used in the CRISPR-Cas9 system, as well as their functions in gene expression alterations that lead to cancer initiation and progression. In addition, we surveyed various species of CRISPR-dead Cas9 (dCas9) systems, a mutant version of Cas9 with no endonuclease activity. Such systems are applicable in epigenetic therapy for gene expression modulation through chemical group editing on nucleosomes and chromatin remodeling, which finally return the cell to the normal status and prevent cancer progression.

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