DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults

Obesity is a major risk factor for cardiovascular disease. We previously demonstrated impaired vascular function that correlated with global DNA hypomethylation in adipose tissue (AT) isolated from obese adults (OB). Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers and stand as an unexploited precision medicine reserve. Hypothesis: We hypothesized a contributing role of DNA methylation to systemic inflammation in OB subjects compared to lean controls (CON). We also explored the correlation between these methylation profiles and cardiometabolic measurements. Methods: We obtained blood and AT samples from bariatric patients (n=24; age: 36±7 yrs; BMI: 50.7±8.7 kg/m2) and CON adults (n=24; age: 36±2 yrs; BMI: 25.8±1 kg/m2). AT-isolated arterioles were tested for flow-induced dilation (FID), nitric oxide (NO) and reactive oxygen species (ROS) production. Brachial artery flow-mediated dilation (FMD) was measured via Doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity (EpiTect Methyl II PCR Arrays) were analyzed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. Results: 70% of genes had a higher methylated fraction in CON compare to only 28% in OB subjects. After correction for multiple testing, 28 genes were significantly hypermethylated in CON compared to OB; on top of these genes are CXCL1, CXCL12, CXCL6, EGR1, HDAC4, IGF2BP2, IL12A, IL12B, and IL17RA. Ten of these genes had significantly higher mRNA in OB compared to CON indicating the functional impact of such signals on gene transcription; on top of these genes are CXCL6, TLR5, IL6ST, IL15RA, and HDAC4. Methylation % of differentially methylated genes inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and CRP (C-reactive protein), arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Conclusions: Our results suggest that vascular dysfunction in OB adults may be attributed to aberrant DNA methylation. A downstream target for this pathway could reside in endothelial cells resulting in vascular dysfunction

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Integrated analysis of DNA methylation profile in HLA-G gene and imaging in coronary heart disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.1255 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

G Benincasa ◽

C Schiano ◽

T Infante ◽

M Franzese ◽

R Casale ◽

...

Keyword(s):

Dna Methylation ◽

Coronary Heart Disease ◽

Heart Disease ◽

Cpg Island ◽

Methylation Profile ◽

Integrated Analysis ◽

Funding Source ◽

Relevant Parameter ◽

Cardiac Computed Tomography Angiography ◽

Dna Methylation Profile

Abstract Aims Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups. Conclusions Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health

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DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Communications Biology ◽

10.1038/s42003-020-01469-0 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Vanessa Lakis ◽

◽

Rita T. Lawlor ◽

Felicity Newell ◽

Ann-Marie Patch ◽

...

Keyword(s):

Dna Methylation ◽

Neuroendocrine Tumors ◽

Methylation Profile ◽

Pancreatic Neuroendocrine Tumors ◽

Wild Type ◽

Genomic Information ◽

Chromosome 11 ◽

Dna Methylation Profile ◽

Methylation Patterns ◽

Recurrent Patterns

AbstractHere we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.

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Overlapping DNA methylation profile between placentas with trisomy 16 and early-onset preeclampsia

Placenta ◽

10.1016/j.placenta.2014.01.001 ◽

2014 ◽

Vol 35 (3) ◽

pp. 216-222 ◽

Cited By ~ 16

Author(s):

J.D. Blair ◽

S. Langlois ◽

D.E. McFadden ◽

W.P. Robinson

Keyword(s):

Dna Methylation ◽

Early Onset ◽

Methylation Profile ◽

Trisomy 16 ◽

Dna Methylation Profile ◽

Early Onset Preeclampsia

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Active BRAF-V600E is the key player in generation of a sessile serrated polyp-specific DNA methylation profile

PLoS ONE ◽

10.1371/journal.pone.0192499 ◽

2018 ◽

Vol 13 (3) ◽

pp. e0192499 ◽

Cited By ~ 4

Author(s):

Somaye Dehghanizadeh ◽

Vahid Khoddami ◽

Timothy L. Mosbruger ◽

Sue S. Hammoud ◽

Kornelia Edes ◽

...

Keyword(s):

Dna Methylation ◽

Methylation Profile ◽

Braf V600e ◽

Serrated Polyp ◽

Dna Methylation Profile

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Methylome and transcriptome analyses of soybean response to bean pyralid larvae

BMC Genomics ◽

10.1186/s12864-021-08140-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wei-Ying Zeng ◽

Yu-Rong Tan ◽

Sheng-Feng Long ◽

Zu-Dong Sun ◽

Zhen-Guang Lai ◽

...

Keyword(s):

Dna Methylation ◽

Protein Biosynthesis ◽

Cell Structure ◽

Methylation Profile ◽

Primary Metabolism ◽

Global Methylation ◽

Genome Wide ◽

Differentially Methylated Genes ◽

Dna Methylation Profile ◽

Soybean Resistance

Abstract Background Bean pyralid is one of the major leaf-feeding insects that affect soybean crops. DNA methylation can control the networks of gene expressions, and it plays an important role in responses to biotic stress. However, at present the genome-wide DNA methylation profile of the soybean resistance to bean pyralid has not been reported so far. Results Using whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq), we analyzed the highly resistant material (Gantai-2-2, HRK) and highly susceptible material (Wan82–178, HSK), under bean pyralid larvae feeding 0 h and 48 h, to clarify the molecular mechanism of the soybean resistance and explore its insect-resistant genes. We identified 2194, 6872, 39,704 and 40,018 differentially methylated regions (DMRs), as well as 497, 1594, 9596 and 9554 differentially methylated genes (DMGs) in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48 comparisons, respectively. Through the analysis of global methylation and transcription, 265 differentially expressed genes (DEGs) were negatively correlated with DMGs, there were 34, 49, 141 and 116 negatively correlated genes in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48, respectively. The MapMan cluster analysis showed that 114 negatively correlated genes were clustered in 24 pathways, such as protein biosynthesis and modification; primary metabolism; secondary metabolism; cell cycle, cell structure and component; RNA biosynthesis and processing, and so on. Moreover, CRK40; CRK62; STK; MAPK9; L-type lectin-domain containing receptor kinase VIII.2; CesA; CSI1; fimbrin-1; KIN-14B; KIN-14 N; KIN-4A; cytochrome P450 81E8; BEE1; ERF; bHLH25; bHLH79; GATA26, were likely regulatory genes involved in the soybean responses to bean pyralid larvae. Finally, 5 DMRs were further validated that the genome-wide DNA data were reliable through PS-PCR and 5 DEGs were confirmed the relationship between DNA methylation and gene expression by qRT-PCR. The results showed an excellent agreement with deep sequencing. Conclusions Genome-wide DNA methylation profile of soybean response to bean pyralid was obtained for the first time. Several specific DMGs which participated in protein kinase, cell and organelle, flavonoid biosynthesis and transcription factor were further identified to be likely associated with soybean response to bean pyralid. Our data will provide better understanding of DNA methylation alteration and their potential role in soybean insect resistance.

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Chicken cecal DNA methylome alteration in the response to Salmonella enterica serovar Enteritidis inoculation

10.21203/rs.3.rs-20344/v2 ◽

2020 ◽

Author(s):

Yuanmei Wang ◽

Liying Liu ◽

Min Li ◽

Lili Lin ◽

Pengcheng Su ◽

...

Keyword(s):

Dna Methylation ◽

Signaling Pathway ◽

Salmonella Enterica ◽

Methylation Profile ◽

Control Group ◽

Poultry Production ◽

Salmonella Enterica Serovar Enteritidis ◽

Genome Wide ◽

Differentially Methylated Genes ◽

Dna Methylation Profile

Abstract Background: Salmonella enterica serovar Enteritidis (SE) is one of the pathogenic bacteria, which affects poultry production and poses a severe threat to public health. Chicken meat and eggs are the main sources of human salmonellosis. DNA methylation is involved in regulatory processes including gene expression, chromatin structure and genomic imprinting. To understand the methylation regulation in the response to SE inoculation in chicken, the genome-wide DNA methylation profile following SE inoculation was analyzed through whole-genome bisulfite sequencing in the current study.Results: There were 185,362,463 clean reads and 126,098,724 unique reads in the control group, and 180,530,750 clean Reads and 126,782,896 unique reads in the inoculated group. The methylation density in the gene body was higher than that in the upstream and downstream regions of the gene. There were 8,946 differentially methylated genes (3,639 hypo-methylated genes, 5,307 hyper-methylated genes) obtained between inoculated and control groups. Methylated genes were mainly enriched in immune-related Gene Ontology (GO) terms and metabolic process terms. Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, FoxO signaling pathway, Wnt signaling pathway and several metabolism-related pathways were significantly enriched. The density of differentially methylated cytosines in miRNAs was the highest. HOX genes were widely methylated.Conclusions: The genome-wide DNA methylation profile in the response to SE inoculation in chicken was analyzed. SE inoculation promoted the DNA methylation in the chicken cecum and caused methylation alteration in immune- and metabolic- related genes. Wnt signal pathway, miRNAs and HOX gene family may play crucial roles in the methylation regulation of SE inoculation in chicken. The findings herein will deepen the understanding of epigenetic regulation in the response to SE inoculation in chicken.

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