scholarly journals Genome-wide identification of DNA methylation provides insights into the association of gene expression in rice exposed to pesticide atrazine

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


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.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 214.1-214
Author(s):  
I. Arias de la Rosa ◽  
M. D. López Montilla ◽  
J. Rodríguez ◽  
E. Ballester ◽  
C. Torres-Granados ◽  
...  

Background:Cardiovascular risk factors are increased in Psoriatic Arthritis (PsA). In fact, around 60% out of PsA patients display insulin resistance (IR), a hallmark of metabolic syndrome, which might significantly contribute to the cardiovascular disease. Latest studies suggested that inflammatory and metabolic disorders may be under epigenetic control, including DNA methylation. DNA methylation is an unexplored area in the field of PsA.Objectives:To study the alterations in the genome-wide DNA methylation profile of CD4+T cells from PsA patients and its relationship with its pathology and the risk of cardiovascular comorbidity.Methods:Twenty healthy controls (HC) and 20 PsA patients were included in the study. PsA patients were classified into insulin resistant and non-insulin resistant according to HOMA-IR index. CD4+T lymphocytes were isolated from peripheral blood by positive immunomagnetic selection. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs (TSS1500, TSS200, 5UTR, 3UTR, first exon, gene body). Beta values (β) estimating methylation levels were obtained at each CpG site, and differentially methylated genes (DMG) between PsA and HC were identified. Functional classification of these genes was carried out through gene ontology analysis (PANTHER database). Gene expression analysis of the selected genes was also evaluated by RT-PCR. Vascular parameters including carotid intima-media thickness (cIMT) and endothelial function was analyzed by ecodoppler and periflux respectively.Results:The genome-wide methylation analysis identified 112 DMGs including 41 hypomethylated and 71 hypermethylated. These differentially methylated genes were enriched with several signaling pathways and disease categories including immune response, metabolic processes, oxidative stress, vascular and inflammatory pathways. The altered gene expression of selected genes with altered methylation levels in PsA was also validated. Correlation and association analysis of these DMGs with clinical and analytical variables, cardiovascular risk factors and endothelial microvascular function revealed that the degree of methylation of these genes was significantly associated with cIMT (IGF1R, NDRG3, SMYD3, HLA-DRB1, WDR70), arterial pressure (METT5D1, NRDG3, ADAM17, SMYD3, WNK1, CBX1), insulin resistance (AKAP13, SEMA6D, PLCB1), altered lipid profile and atherogenic index (MYBL1, METT5D1, MAN2A1, SLC1A7, SEMA6D, PLCB1, TLK1, SDK1, CBX1), inflammation (MYBL1, NDUFA5, METT5D1, SEMA6D, PLCB1, TLK1), and endothelial dysfunction (ADAMST10, GPCPD1, CCDC88A). In addition, this analysis also identified 435 DMGs including 280 hypomethylated and 155 hypermethylated in CD4+T cells from IR-PsA vs non IR-PsA patients. Between these two groups of PsA patients, CHUK, SERINC1, RUNX1, TTYH2, TXNDC11, FAF1, BICD1, SCD5, PDE5A, FAS, NFIA and GRP75 displayed the most significantly altered methylation, suggesting the role of these genes in the metabolic complications associated with PsA.Conclusion:These findings help our understanding of the pathogenesis of PsA and advance epigenetic studies in regards to this disease and the cardiometabolic comorbidities associated. Funded by ISCIII (PI17/01316 and RIER RD16/0012/0015) co-funded with FEDER.Disclosure of Interests:Iván Arias de la Rosa: None declared, María Dolores López Montilla Speakers bureau: Celgene, Javier Rodríguez: None declared, Esteban Ballester: None declared, Carmen Torres-Granados: None declared, Carlos Perez-Sanchez: None declared, Maria del Carmen Abalos-Aguilera: None declared, Gómez García Ignacio: None declared, Desiree Ruiz: None declared, Alejandra M. Patiño-Trives: None declared, María Luque-Tévar: None declared, Eduardo Collantes-Estévez Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE, Lilly, Bristol and Celgene., Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer., Alejandro Escudero Contreras Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene., Nuria Barbarroja Puerto Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE and Celgene.


Plants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 135 ◽  
Author(s):  
Zhongyuan Lin ◽  
Meihui Liu ◽  
Rebecca Njeri Damaris ◽  
Tonny Maraga Nyong’a ◽  
Dingding Cao ◽  
...  

DNA methylation is a vital epigenetic modification. Methylation has a significant effect on the gene expression influencing the regulation of different physiological processes. Current studies on DNA methylation have been conducted on model plants. Lotus (Nelumbo nucifera) is a basic eudicot exhibiting variations during development, especially in flower formation. DNA methylation profiling was conducted on different flower tissues of lotuses through whole genome bisulfite sequencing (WGBS) to investigate the effects of DNA methylation on its stamen petaloid. A map of methylated cytosines at the single base pair resolution for the lotus was constructed. When the stamen was compared with the stamen petaloid, the DNA methylation exhibited a global decrease. Genome-wide relationship analysis between DNA methylation and gene expression identified 31 different methylation region (DMR)-associated genes, which might play crucial roles in floral organ formation, especially in the stamen petaloid. One out of 31 DMR-associated genes, NNU_05638 was homolog with Plant U-box 33 (PUB33). The DNA methylation status of NNU_05638 promoter was distinct in three floral organs, which was confirmed by traditional bisulfite sequencing. These results provide further insights about the regulation of stamen petaloids at the epigenetic level in lotus.


2020 ◽  
Vol 21 (12) ◽  
pp. 4476
Author(s):  
Marcela A S Pinhel ◽  
Natália Y Noronha ◽  
Carolina F Nicoletti ◽  
Vanessa AB Pereira ◽  
Bruno AP de Oliveira ◽  
...  

Weight regulation and the magnitude of weight loss after a Roux-en-Y gastric bypass (RYGB) can be genetically determined. DNA methylation patterns and the expression of some genes can be altered after weight loss interventions, including RYGB. The present study aimed to evaluate how the gene expression and DNA methylation of PIK3R1, an obesity and insulin-related gene, change after RYGB. Blood samples were obtained from 13 women (35.9 ± 9.2 years) with severe obesity before and six months after surgical procedure. Whole blood transcriptome and epigenomic patterns were assessed by microarray-based, genome-wide technologies. A total of 1966 differentially expressed genes were identified in the pre- and postoperative periods of RYGB. From these, we observed that genes involved in obesity and insulin pathways were upregulated after surgery. Then, the PIK3R1 gene was selected for further RT-qPCR analysis and cytosine-guanine nucleotide (CpG) sites methylation evaluation. We observed that the PI3KR1 gene was upregulated, and six DNA methylation CpG sites were differently methylated after bariatric surgery. In conclusion, we found that RYGB upregulates genes involved in obesity and insulin pathways.


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