scholarly journals Mild drought in the vegetative stage induces phenotypic, gene expression, and DNA methylation plasticity in Arabidopsis but no transgenerational effects

2020 ◽  
Vol 71 (12) ◽  
pp. 3588-3602 ◽  
Author(s):  
Tom J M Van Dooren ◽  
Amanda Bortolini Silveira ◽  
Elodie Gilbault ◽  
José M Jiménez-Gómez ◽  
Antoine Martin ◽  
...  

Abstract There is renewed interest in whether environmentally induced changes in phenotypes can be heritable. In plants, heritable trait variation can occur without DNA sequence mutations through epigenetic mechanisms involving DNA methylation. However, it remains unknown whether this alternative system of inheritance responds to environmental changes and if it can provide a rapid way for plants to generate adaptive heritable phenotypic variation. To assess potential transgenerational effects induced by the environment, we subjected four natural accessions of Arabidopsis thaliana together with the reference accession Col-0 to mild drought in a multi-generational experiment. As expected, plastic responses to drought were observed in each accession, as well as a number of intergenerational effects of the parental environments. However, after an intervening generation without stress, except for a very few trait-based parental effects, descendants of stressed and non-stressed plants were phenotypically indistinguishable irrespective of whether they were grown in control conditions or under water deficit. In addition, genome-wide analysis of DNA methylation and gene expression in Col-0 demonstrated that, while mild drought induced changes in the DNA methylome of exposed plants, these variants were not inherited. We conclude that mild drought stress does not induce transgenerational epigenetic effects.

2018 ◽  
Author(s):  
Tom JM Van Dooren ◽  
Amanda Bortolini Silveira ◽  
Elodie Gilbault ◽  
José M. Jiménez-Gómez ◽  
Antoine Martin ◽  
...  

SummaryWhether environmentally induced changes in phenotypes can be heritable is a topic with revived interest, in part because of observations in plants that heritable trait variation can occur without DNA sequence mutations. This other system of inheritance, called transgenerational epigenetics, typically involves differences in DNA methylation that are stable across multiple generations. However, it remains unknown if such a system responds to environmental changes and if it could therefore provide a rapid way for plants to generate adaptive heritable phenotypic variation. Here, we used a well-controlled phenotyping platform and whole-genome bisulfite sequencing to investigate potential heritable effects of mild drought applied over two successive generations in Arabidopsis thaliana. Plastic phenotypic responses were observed in plants exposed to drought. After an intervening generation without stress, descendants of stressed and non-stressed plants were phenotypically indistinguishable, except for very few trait-based parental effects, and irrespective of whether they were grown in control conditions or under water deficit. Moreover, while mild drought induced changes to the DNA methylome of exposed plants, DNA methylation variants were not inherited. These findings add to the growing body of evidence indicating that transgenerational epigenetics is not a common response of plants to environmental changes.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1413
Author(s):  
Mariana Lizbeth Rodríguez-López ◽  
José Jaime Martínez-Magaña ◽  
David Ruiz-Ramos ◽  
Ana Rosa García ◽  
Laura Gonzalez ◽  
...  

Binge-eating disorder, recently accepted as a diagnostic category, is differentiated from bulimia nervosa in that the former shows the presence of binge-eating episodes and the absence of compensatory behavior. Epigenetics is a conjunct of mechanisms (like DNA methylation) that regulate gene expression, which are dependent on environmental changes. Analysis of DNA methylation in eating disorders shows that it is reduced. The present study aimed to analyze the genome-wide DNA methylation differences between individuals diagnosed with BED and BN. A total of 46 individuals were analyzed using the Infinium Methylation EPIC array. We found 11 differentially methylated sites between BED- and BN-diagnosed individuals, with genome-wide significance. Most of the associations were found in genes related to metabolic processes (ST3GAL4, PRKAG2, and FRK), which are hypomethylated genes in BED. Cg04781532, located in the body of the PRKAG2 gene (protein kinase AMP-activated non-catalytic subunit gamma 2), was hypomethylated in individuals with BED. Agonists of PRKAG2, which is the subunit of AMPK (AMP-activated protein kinase), are proposed to treat obesity, BED, and BN. The present study contributes important insights into the effect that BED could have on PRKAG2 activation.


2020 ◽  
Vol 14 ◽  
Author(s):  
Mette Soerensen ◽  
Dominika Marzena Hozakowska-Roszkowska ◽  
Marianne Nygaard ◽  
Martin J. Larsen ◽  
Veit Schwämmle ◽  
...  

Epigenomics ◽  
2021 ◽  
Author(s):  
Beatriz Garcia-Ruiz ◽  
Manuel Castro de Moura ◽  
Gerard Muntané ◽  
Lourdes Martorell ◽  
Elena Bosch ◽  
...  

Aim: To investigate DDR1 methylation in the brains of bipolar disorder (BD) patients and its association with DDR1 mRNA levels and comethylation with myelin genes. Materials & methods: Genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) corrected for glial composition and DDR1 gene expression analysis in the occipital cortices of individuals with BD (n = 15) and healthy controls (n = 15) were conducted. Results: DDR1 5-methylcytosine levels were increased and directly associated with DDR1b mRNA expression in the brains of BD patients. We also observed that DDR1 was comethylated with a group of myelin genes. Conclusion: DDR1 is hypermethylated in BD brain tissue and is associated with isoform expression. Additionally, DDR1 comethylation with myelin genes supports the role of this receptor in myelination.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jessilyn Dunn ◽  
Haiwei Qiu ◽  
Soyeon Kim ◽  
Daudi Jjingo ◽  
Ryan Hoffman ◽  
...  

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.


Author(s):  
Dan Sun ◽  
Thomas S. Layman ◽  
Hyeonsoo Jeong ◽  
Paramita Chatterjee ◽  
Kathleen Grogan ◽  
...  

ABSTRACTDNA methylation is known to play critical roles in key biological processes. Most of our knowledge on regulatory impacts of DNA methylation has come from laboratory-bred model organisms, which may not exhibit the full extent of variation found in wild populations. Here, we investigated naturally-occurring variation in DNA methylation in a wild avian species, the white-throated sparrow (Zonotrichia albicollis). This species offers exceptional opportunities for studying the link between genetic differentiation and phenotypic traits because of a non-recombining chromosome pair linked to both plumage and behavioral phenotypes. Using novel single-nucleotide resolution methylation maps and gene expression data, we show that DNA methylation and the expression of DNA methyltransferases are significantly higher in adults than in nestlings. Genes for which DNA methylation varied between nestlings and adults were implicated in development and cell differentiation and were located throughout the genome. In contrast, differential methylation between plumage morphs was localized to the non-recombining chromosome pair. One subset of CpGs on the non-recombining chromosome was extremely hypomethylated and localized to transposable elements. Changes in methylation predicted changes in gene expression for both chromosomes. In summary, we demonstrate changes in genome-wide DNA methylation that are associated with development and with specific functional categories of genes in white-throated sparrows. Moreover, we observe substantial DNA methylation reprogramming associated with the suppression of recombination, with implications for genome integrity and gene expression divergence. These results offer an unprecedented view of ongoing epigenetic reprogramming in a wild population.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250013
Author(s):  
Chia-Hsin Hsu ◽  
Hirotaka Tomiyasu ◽  
Chi-Hsun Liao ◽  
Chen-Si Lin

Doxorubicin resistance is a major challenge in the successful treatment of canine diffuse large B-cell lymphoma (cDLBCL). In the present study, MethylCap-seq and RNA-seq were performed to characterize the genome-wide DNA methylation and differential gene expression patterns respectively in CLBL-1 8.0, a doxorubicin-resistant cDLBCL cell line, and in CLBL-1 as control, to investigate the underlying mechanisms of doxorubicin resistance in cDLBCL. A total of 20289 hypermethylated differentially methylated regions (DMRs) were detected. Among these, 1339 hypermethylated DMRs were in promoter regions, of which 24 genes showed an inverse correlation between methylation and gene expression. These 24 genes were involved in cell migration, according to gene ontology (GO) analysis. Also, 12855 hypermethylated DMRs were in gene-body regions. Among these, 353 genes showed a positive correlation between methylation and gene expression. Functional analysis of these 353 genes highlighted that TGF-β and lysosome-mediated signal pathways are significantly associated with the drug resistance of CLBL-1. The tumorigenic role of TGF-β signaling pathway in CLBL-1 8.0 was further validated by treating the cells with a TGF-β inhibitor(s) to show the increased chemo-sensitivity and intracellular doxorubicin accumulation, as well as decreased p-glycoprotein expression. In summary, the present study performed an integrative analysis of DNA methylation and gene expression in CLBL-1 8.0 and CLBL-1. The candidate genes and pathways identified in this study hold potential promise for overcoming doxorubicin resistance in cDLBCL.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yi Chen Lu ◽  
Sheng Jun Feng ◽  
Jing Jing Zhang ◽  
Fang Luo ◽  
Shuang Zhang ◽  
...  

2016 ◽  
Vol 214 (1) ◽  
pp. S136-S137
Author(s):  
Hye J. Heo ◽  
Jessica Tozour ◽  
Fabien Delahaye ◽  
Yongmei Zhao ◽  
Lingguang Cui ◽  
...  

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Xiaoling Wang ◽  
Yue Pan ◽  
Haidong Zhu ◽  
Guang Hao ◽  
Xin Wang ◽  
...  

Background: Several large-scale epigenome wide association studies on obesity-related DNA methylation changes have been published and in total identified 46 CpG sites. These studies were conducted in middle-aged and older adults of Caucasians and African Americans (AAs) using leukocytes. To what extend these signals are independent of cell compositions as well as to what extend they may influence gene expression have not been systematically investigated. Furthermore, the high prevalence of obesity comorbidities in middle-aged or older population may hide or bias obesity itself related DNA methylation changes. Methods: In this study of healthy AA youth and young adults, genome wide DNA methylation data from leukocytes were obtained from three independent studies: EpiGO study (96 obese cases vs. 92 lean controls, aged 14-21, 50% females, test of interest is obesity status), LACHY study (284 participants from general population, aged 14-18, 50% females, test of interest is BMI), and Georgia Stress and Heart study (298 participants from general population, aged 18-38, 52% females, test of interest is BMI) using the Infinium HumanMethylation450 BeadChip. Genome wide DNA methylation data from purified neutrophils as well as genome wide gene expression data from leukocytes using Illumina HT12 V4 array were also obtained for the EpiGO samples. Results: The meta-analysis on the 3 cohorts identified 76 obesity related CpG sites in leukocytes with p<1х10 -7 . Out of the 46 previously identified CpG sites, 36 can be replicated in this AA youth and young adult sample with same direction and p<0.05. Out of the 107 CpG sites including the 36 replicated ones and the 71 newly identified ones, 71 CpG sites (66%) had their relationship with obesity replicated in purified neutrophils (p<0.05). The analysis on the cis regulation of the 107 CpG sites on gene expression showed that 59 CpG sites had at least one gene within 250kb having expression difference between obese cases and lean controls. Furthermore, out of the 59 CpG sites, 6 showed significantly negative correlations and 1 showed significantly positive correlation with the differentially expressed genes. These CpG sites located in SOCS3, CISH, ABCG1, PIM3 and PTGDS genes. Conclusion: In this study of AA youth and young adults, we identified novel CpG sites associated with obesity and replicated majority of the CpG sites previously identified in middle-aged and older adults. For the first time, we showed that majority of the obesity related CpG sites identified from leukocytes are not driven by cell compositions and provided the direct link between DNA methylation-gene expression-obesity status for 7 CpG sites in 5 genes.


Sign in / Sign up

Export Citation Format

Share Document