Potato cytosine methylation and gene expression changes induced by a beneficial bacterial endophyte, Burkholderia phytofirmans strain PsJN

AbstractCytosine methylation is an epigenetically heritable DNA modification common in plant and animal genes, but the functional and evolutionary significance of gene body methylation (gbM) has remained enigmatic. Here we show that gbM enhances gene expression in Arabidopsis thaliana. We also demonstrate that natural gbM variation influences drought and heat tolerance and flowering time by modulating gene expression, including that of Flowering Locus C (FLC). Notably, epigenetic variation accounts for as much trait heritability in natural populations as DNA sequence polymorphism. Furthermore, we identify gbM variation in numerous genes associated with environmental variables, including a strong association between flowering time, spring atmospheric NO2 – a by-product of fossil fuel burning – and FLC epialleles. Our study demonstrates that gbM is an important modulator of gene expression, and its natural variation fundamentally shapes phenotypic diversity in plant populations. Thus, gbM provides an epigenetic basis for adaptive evolution independent of genetic polymorphism.

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Silencing of Mutator Elements in Maize Involves Distinct Populations of Small RNAs and Distinct Patterns of DNA Methylation

Genetics ◽

10.1534/genetics.120.303033 ◽

2020 ◽

Vol 215 (2) ◽

pp. 379-391 ◽

Cited By ~ 3

Author(s):

Diane Burgess ◽

Hong Li ◽

Meixia Zhao ◽

Sang Yeol Kim ◽

Damon Lisch

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Small Rnas ◽

Cytosine Methylation ◽

De Novo ◽

Epigenetic Silencing ◽

Inverted Repeats ◽

Causal Relationships ◽

Terminal Inverted Repeats ◽

Silencing Pathways

Transposable elements (TEs) are a ubiquitous feature of plant genomes. Because of the threat they post to genome integrity, most TEs are epigenetically silenced. However, even closely related plant species often have dramatically different populations of TEs, suggesting periodic rounds of activity and silencing. Here, we show that the process of de novo methylation of an active element in maize involves two distinct pathways, one of which is directly implicated in causing epigenetic silencing and one of which is the result of that silencing. Epigenetic changes involve changes in gene expression that can be heritably transmitted to daughter cells in the absence of changes in DNA sequence. Epigenetics has been implicated in phenomena as diverse as development, stress response, and carcinogenesis. A significant challenge facing those interested in investigating epigenetic phenomena is determining causal relationships between DNA methylation, specific classes of small RNAs, and associated changes in gene expression. Because they are the primary targets of epigenetic silencing in plants and, when active, are often targeted for de novo silencing, TEs represent a valuable source of information about these relationships. We use a naturally occurring system in which a single TE can be heritably silenced by a single derivative of that TE. By using this system it is possible to unravel causal relationships between different size classes of small RNAs, patterns of DNA methylation, and heritable silencing. Here, we show that the long terminal inverted repeats within Zea mays MuDR transposons are targeted by distinct classes of small RNAs during epigenetic silencing that are dependent on distinct silencing pathways, only one of which is associated with transcriptional silencing of the transposon. Further, these small RNAs target distinct regions of the terminal inverted repeats, resulting in different patterns of cytosine methylation with different functional consequences with respect to epigenetic silencing and the heritability of that silencing.

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Changes of cytosine methylation induced by wide hybridization and allopolyploidy in Cucumis

Genome ◽

10.1139/g08-063 ◽

2008 ◽

Vol 51 (10) ◽

pp. 789-799 ◽

Cited By ~ 22

Author(s):

Longzheng Chen ◽

Jinfeng Chen

Keyword(s):

Gene Expression ◽

Cytosine Methylation ◽

Polymerase Chain Reaction Analysis ◽

Methylation Pattern ◽

Functional Genes ◽

Chain Reaction ◽

Polymerase Chain ◽

Phenotypic Variations ◽

Parent Observations ◽

Or Genes

We previously demonstrated that allopolyploidization could induce phenotypic variations and genome changes in a newly synthesized allotetraploid in Cucumis . To explore the molecular involvement of epigenetic phenomena, we investigated cytosine methylation in Cucumis by using methylation-sensitive amplified polymorphism (MSAP). Results revealed a twofold difference in the level of cytosine methylation between the reciprocal F1 hybrids and the allotetraploid. Analysis of the methylation pattern indicated that methylation changed at 2.0% to 6.4% of total sites in both the F1 hybrids and the allotetraploid compared with their corresponding parents. Furthermore, 68.2% to 80.0% of the changed sites showed an increase in cytosine methylation and a majority of the methylated sites were from the maternal parent. Observations in different generations of the allotetraploid found that the extent of change in cytosine methylation pattern between the S1 and S2 was significantly higher than that between the S2 and S3, suggesting stability in advanced generations. Analysis of 7 altered sequences indicated their similarity to known functional genes or genes involved in regulating gene expression. Reverse transcription – polymerase chain reaction analysis suggested that at least two of the methylation changes might be related to gene expression changes, which further supports the hypothesis that DNA methylation plays a significant role in allopolyploidization.

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The Role of Epigenetic Alterations in Papillary Thyroid Carcinogenesis

Journal of Thyroid Research ◽

10.4061/2011/895470 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

Ogechukwu P. Eze ◽

Lee F. Starker ◽

Tobias Carling

Keyword(s):

Gene Expression ◽

Cytosine Methylation ◽

Cpg Islands ◽

Tumor Development ◽

Genetic Alterations ◽

Papillary Thyroid ◽

Promoter Regions ◽

Novel Technologies ◽

Approaches To Study ◽

Thyroid Malignancies

Papillary thyroid carcinoma (PTC) accounts for over 80% of all thyroid malignancies. The molecular pathogenesis remains incompletely clarified although activation of the RET fusion oncogenes, and RAS and BRAF oncogenes, has been well characterized. Novel technologies using genome-wide approaches to study tumor genomes and epigenomes have provided great insights into tumor development. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause altered patterns of gene expression/function. It has been established beyond doubt that promoter cytosine methylation in CpG islands, and the subsequent gene silencing, is intimately involved in cancer development. These epigenetic events very likely contribute to significant variation in gene expression profiling, phenotypic features, and biologic characteristics seen in PTC. Hypermethylation of promoter regions has also been analyzed in PTC, and most studies have focused on individual genes or a small cohort of genes implicated in tumorigenesis.

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The contrasting response to drought and waterlogging is underpinned by divergent DNA methylation programs associated with gene expression in sesame

10.1101/362905 ◽

2018 ◽

Author(s):

Komivi Dossa ◽

Marie Ali Mmadi ◽

Rong Zhou ◽

Qi Zhou ◽

Mei Yang ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Abiotic Stresses ◽

Cytosine Methylation ◽

De Novo ◽

Recovery Phase ◽

Epigenetic Mechanism ◽

Drought Tolerant ◽

Sesame Genotypes ◽

Methylation Patterns

AbstractDNA methylation is a heritable epigenetic mechanism that participates in gene regulation under abiotic stresses in plants. Sesame (Sesamum indicum L.) is typically considered a drought-tolerant crop but highly susceptible to waterlogging, a property attributed to its presumed origin in Africa or India. Understanding DNA methylation patterns in sesame under drought and waterlogging conditions can provide insights into the regulatory mechanisms underlying its contrasting responses to these principal abiotic stresses. Here, we combined Methylation-Sensitive Amplified Polymorphism and transcriptome analyses to profile cytosine methylation patterns, gene expression alteration, and their interplay in drought-tolerant and waterlogging-tolerant sesame genotypes under control, stress and recovery conditions. Our data showed that drought stress strongly induced de novo methylation (DNM) whereas most of the loci were demethylated (DM) during the recovery phase. In contrast, waterlogging decreased the level of methylation under stress but during the recovery phase, both DM and DNM were concomitantly deployed. In both stresses, the differentially expressed genes (DEGs) were highly correlated with the methylation patterns. We observed that DM was associated with the up-regulation of the DEGs while DNM was correlated with the down-regulation of the DEGs. In addition, we sequenced 44 differentially methylated regions of which 90% overlapped with the promoters and coding sequences of the DEGs. Altogether, we demonstrated that sesame has divergent epigenetic programs that respond to drought and waterlogging stresses. Our results also highlighted the possible interplay among DNA methylation and gene expression, which may modulate the contrasting responses to drought and waterlogging in sesame.

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Integrative Network Analysis of Differentially Methylated and Expressed Genes for Biomarker Identification in Leukemia

10.1101/658948 ◽

2019 ◽

Author(s):

Robersy Sanchez ◽

Sally A. Mackenzie

Keyword(s):

Gene Expression ◽

Signaling Pathway ◽

Cytosine Methylation ◽

Complex Disease ◽

Lymphoblastic Leukemia ◽

Integrated Analysis ◽

Ras Signaling ◽

Protein Protein Interaction ◽

Diagnosis And Prognosis ◽

Ppi Networks

AbstractGenome-wide DNA methylation and gene expression are commonly altered in pediatric acute lymphoblastic leukemia (PALL). Integrated analysis of cytosine methylation and expression datasets has the potential to provide deeper insights into the complex disease states and their causes than individual disconnected analyses. Studies of protein-protein interaction (PPI) networks of differentially methylated (DMGs) and expressed genes (DEGs) showed that gene expression and methylation consistently targeted the same gene pathways associated with cancer: Pathways in cancer, Ras signaling pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway, among others. Detected gene hubs and hub sub-networks are integrated by signature loci associated with cancer that include, for example, NOTCH1, RAC1, PIK3CD, BCL2, and EGFR. Statistical analysis disclosed a stochastic deterministic dependence between methylation and gene expression within the set of genes simultaneously identified as DEGs and DMGs, where larger values of gene expression changes are probabilistically associated with larger values of methylation changes. Concordance analysis of the overlap between enriched pathways in DEG and DMG datasets revealed statistically significant agreement between gene expression and methylation changes, reflecting a coordinated response of methylation and gene-expression regulatory systems. These results support the identification of reliable and stable biomarkers for cancer diagnosis and prognosis.

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Distinct Cytosine Modification Profiles Define Epithelial-to-Mesenchymal Cell-State Transitions

10.21203/rs.3.rs-823460/v1 ◽

2021 ◽

Author(s):

Min Kyung Lee ◽

Meredith S. Brown ◽

Owen Wilkins ◽

Diwakar R. Pattabiraman ◽

Brock C. Christensen

Keyword(s):

Gene Expression ◽

Cytosine Methylation ◽

Epithelial To Mesenchymal Transition ◽

Mesenchymal Cell ◽

State Transitions ◽

Open Chromatin ◽

Intermediate Cell ◽

Mesenchymal Transition ◽

Accessible Chromatin ◽

Cytosine Modification

Abstract Background: Epithelial-to-mesenchymal transition (EMT) is an early step in the invasion-metastasis cascade, involving progression through a number of cell intermediate states. Due to challenges with isolating intermediate cell states in EMT, genome-wide cytosine modification mechanisms that define transition through EMT states are not completely understood. We measured multiple DNA cytosine methylation modification marks, complemented with chromatin accessibility and gene expression, across clonal populations residing in specific EMT states. Results: Clones exhibiting intermediate EMT phenotypes demonstrated increased global 5-hydroxymethylcytosine (5hmC), decreased 5-methylcytosine (5mC), and more accesible chromatin. Open chromatin regions containing CpG loci with abundant 5hmC were enriched in motifs of key EMT transcription factors, ZEB1 and Snail. The magnitude of altered gene expression in intermediate cell states was higher for genes both with increased gene promoter 5hmC and differentially accessible chromatin compared with genes that exhibited differentially accessible chromatin alone, implicating functional epigenetic duality in regulation of EMT.Conclusion: Our results indicate the importance of both distinct and shared epigenetic profiles at the cytosine and chromatin level associated with EMT processes that contribute to gene regulation and which may be targeted to prevent the progression of EMT.

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Enzymatic Removal of O6-Ethylguanine versus Stability of O4-Ethylthymine in the DNA of Rat Tissues Exposed to the Carcinogen Ethylnitrosourea: Possible Interference of Guanine-O6 Alkylation with 5-Cytosine Methylation in the DNA of Replicating Target Cells

Zeitschrift für Naturforschung C ◽

10.1515/znc-1983-11-1224 ◽

1983 ◽

Vol 38 (11-12) ◽

pp. 1023-1029 ◽

Cited By ~ 19

Author(s):

Rolf Müller ◽

Manfred F. Rajewsky

Keyword(s):

Gene Expression ◽

Cytosine Methylation ◽

Single Pulse ◽

Dna Lesions ◽

Target Cells ◽

Rat Tissues ◽

Kinetics Of ◽

Lung And Kidney

In order to compare the kinetics of their enzymatic elimination from the DNA of liver, kidney, lung, and brain, the alkylation products O4-ethyl-2'-deoxythym idine (O4-EtdThd) and O6-ethyl- 2'-deoxyguanosine (O6-EtdGuo) were quantitated by competitive radioimmunoassay over a period of 48 h after a single pulse of the carcinogen N -ethyl-N-nitrosourea (EtNU ) applied i.p. to 10 and 28-day-old BDIX-rats. The content of O4-EtdThd in the DNA of all organs analyzed remained stable, while O6-EtdGuo (initially formed in DNA with 3 - 4 times higher frequency than O4-EtdThd) was rapidly removed from the DNA of liver, followed by lung and kidney, but persisted strongly in the DNA of brain. At 48 h after the EtNU -pulse, the O4-EtdThd content of liver DNA exceeded the O6-EtdGuo content by about a factor of 4. Since both O6-EtdG uo and O4-EtdThd are miscoding DNA lesions, the lack of enzymatic removal of O4-EtdThd is surprising in view of the apparent concern of cells to restore the integrity of the Opposition of guanine. Genetic consequences more specifically connected with the formation of O6-alkylguanine in DNA might be considered, e.g., possible alterations of gene expression via interference with enzymatic 5-cytosine methylation in 5'-CpG-3' sequences of newly replicated DNA

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The Mechanisms of Generation, Recognition, and Erasure of DNA 5-Methylcytosine and Thymine Oxidations

Journal of Biological Chemistry ◽

10.1074/jbc.r115.656884 ◽

2015 ◽

Vol 290 (34) ◽

pp. 20723-20733 ◽

Cited By ~ 25

Author(s):

Hideharu Hashimoto ◽

Xing Zhang ◽

Paula M. Vertino ◽

Xiaodong Cheng

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Cytosine Methylation ◽

Epigenetic Modifications ◽

Dna Bases ◽

Oxidation States ◽

Control Of Gene Expression ◽

Methylation Of Dna ◽

Recent Developments ◽

Base Excision

One of the most fundamental questions in the control of gene expression in mammals is how the patterns of epigenetic modifications of DNA are generated, recognized, and erased. This includes covalent cytosine methylation of DNA and its associated oxidation states. An array of AdoMet-dependent methyltransferases, Fe(II)- and α-ketoglutarate-dependent dioxygenases, base excision glycosylases, and sequence-specific transcription factors is responsible for changing, maintaining, and interpreting the modification status of specific regions of chromatin. This review focuses on recent developments in characterizing the functional and structural links between the modification status of two DNA bases 5-methylcytosine and thymine (5-methyluracil).

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