scholarly journals Aberrant Hypermethylation of Aldehyde Dehydrogenase 2 Promoter Upstream Sequence in Rats with Experimental Myocardial Infarction

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Peng Wang ◽  
Cheng Shen ◽  
Lei Diao ◽  
Zhiyin Yang ◽  
Fan Fan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Aldehyde Dehydrogenase ◽  
Methylation Level ◽  
Sham Group ◽  
Core Promoter ◽  
Upstream Sequence ◽  
Aldehyde Dehydrogenase 2 ◽  
Cpg Sites

Background. Aldehyde dehydrogenase 2 (ALDH2) plays a crucial role in myocardial protection against ischemia. Downregulation of ALDH2 was evidenced after myocardial infarction and the underlying mechanism is not fully understood. DNA methylation can regulate gene transcription in epigenetic level. We thus hypothesized that DNA methylation may affect ALDH2 expression in myocardial infarction (MI).Methods. MI was induced in Sprague-Dawley rats. MI border zone tissues were harvested at 1st week, 2nd week, and 3rd week after MI. Bisulfite sequencing PCR (BSP) was performed to detect the methylation levels of ALDH2 core promoter. Sequenom MassARRAY platform (MassARRAY) was used to examine the methylation levels of ALDH2 promoter upstream sequence. ALDH2 protein and mRNA expression were assayed by Western blot and real-time PCR, respectively.Results. Compared with Sham group, ALDH2 protein and mRNA expression of MI groups was significantly downregulated. Compared with Sham group, DNA methylation level of CpG sites in ALDH2 promoter upstream sequence was significantly higher in MI groups in a time-dependent manner (CpG1, CpG2, and CpG7,P<0.01). DNA methylation did not affect ALDH2 core promoter sequence during the progress of MI. No significant difference was detected in DNA methylation level of ALDH2 promoter upstream sequence among MI groups.Conclusion. Aberrant hypermethylation of CpG sites in ALDH2 promoter upstream sequence is associated with myocardial ischemia injury and may partly result in ALDH2 downregulation after MI.

scholarly journals DNA Methylation of Pig FUT3 Promoter Alters mRNA Expression to Regulate E. coli F18 Susceptibility

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1586
Author(s):  
Zhengchang Wu ◽  
Dongfeng Shi ◽  
Jian Jin ◽  
Hairui Fan ◽  
Wenbin Bao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Core Promoter ◽  
Inhibitory Effect ◽  
Weaned Piglets ◽  
E Coli ◽  
The Core ◽  
Cpg Sites ◽  
Sp1 Transcription Factor ◽  
Candidate Target

Post-weaning diarrhea (PWD) is frequently associated with E. coli F18 infections in piglets. However, the underlying molecular mechanism concerning the resistance of E. coli F18 in local weaned piglets in China is not clearly understood. In the present study, by a comparative analysis of the transcriptome, a-1,3-fucosyltransferase (FUT3) was evaluated as a key candidate correlated with resistance to E. coli F18 in Sutai and Meishan piglets. Functional analysis demonstrated that FUT3 acts as a key positive regulator of E. coli F18 susceptibility in newly food accustomed piglets. However, the core promoter of FUT3 was present at −500–(−206) bp (chr.2: g.73171117–g.73171616), comprising of 9 methylated CpG sites. Among these, the methylation levels of the two CpG sites (mC-3, mC-5) located in HIF1A and Sp1 transcription factor (TF) considerably associated with mRNA expression of FUT3 (p < 0.05). Our findings indicated that the methylation of mC-3 and mC-5 sites has certain inhibitory effect on FUT3 expression and promotes the resistance of E. coli F18 in piglets. The underlined study may explore FUT3 as a new candidate target in E. coli F18 infection in Chinese local weaned piglets.

scholarly journals Variable DNA methylation of aging-related genes is associated with male COPD

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xizi Du ◽  
Lin Yuan ◽  
Mengping Wu ◽  
Meichao Men ◽  
Ruoxi He ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Differentially Expressed Genes ◽  
Peripheral Blood ◽  
Methylation Level ◽  
Forced Expiratory Volume ◽  
Differentially Expressed ◽  
Control Group ◽  
Cpg Sites ◽  
Copd Patients

Abstract Background Chronic obstructive pulmonary disease (COPD) is a chronic lung inflammatory disease which has a close relationship with aging. Genome-wide analysis reveals that DNA methylation markers vary obviously with age. DNA methylation variations in peripheral blood have the potential to be biomarkers for COPD. However, the specific DNA methylation of aging-related genes in the peripheral blood of COPD patients remains largely unknown. Methods Firstly, 9 aging-related differentially expressed genes (DEGs) in COPD patients were screened out from the 25 aging-related genes profile through a comprehensive screening strategy. Secondly, qPCR and multiple targeted bisulfite enrichment sequencing (MethTarget) were used to detect the mRNA level and DNA methylation level of the 9 differentially expressed genes in the peripheral blood of 60 control subjects and 45 COPD patients. The candidate functional CpG sites were selected on the basis of the regulation ability of the target gene expression. Thirdly, the correlation was evaluated between the DNA methylation level of the key CpG sites and the clinical parameters of COPD patients, including forced expiratory volume in one second (FEV1), forced expiratory volume in one second as percentage of predicted volume (FEV1%), forced expiratory volume/ forced vital capacity (FEV/FVC), modified British medical research council (mMRC) score, acute exacerbation frequency and the situation of frequent of acute aggravation (CAT) score. Lastly, differentially methylated CpG sites unrelated to smoking were also determined in COPD patients. Results Of the 9 differentially expressed aging-related genes, the mRNA expression of 8 genes were detected to be significantly down-regulated in COPD group, compared with control group. Meanwhile, the methylated level of all aging-related genes was changed in COPD group containing 219 COPD-related CpG sites in total. Notably, 27 CpG sites of FOXO3 gene showed a lower False Discovery Rate (FDR) and higher methylation difference values. Also, some variable DNA methylation is associated with the severity of COPD. Additionally, of the 219 COPD-related CpG sites, 147 CpG sites were not related to smoking. Conclusion These results identified that the mRNA expression and DNA methylation level of aging-related genes were changed in male COPD patients, which provides a molecular link between aging and COPD. The identified CpG markers are associated with the severity of COPD and provide new insights into the prediction and identification of COPD.

scholarly journals EGFR DNA Methylation Correlates With EGFR Expression, Immune Cell Infiltration, and Overall Survival in Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhanyu Xu ◽  
Fanglu Qin ◽  
Liqiang Yuan ◽  
Jiangbo Wei ◽  
Yu Sun ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Protein Expression ◽  
Lung Adenocarcinoma ◽  
Methylation Level ◽  
Promoter Region ◽  
Body Region ◽  
Gene Body ◽  
Immune Infiltration ◽  
Cpg Sites ◽  
Gene Body Region

BackgroundThe epidermal growth factor receptor (EGFR) is a primary target of molecular targeted therapy for lung adenocarcinoma (LUAD). The mechanisms that lead to epigenetic abnormalities of EGFR in LUAD are still unclear. The purpose of our study was to evaluate the abnormal methylation of EGFR CpG sites as potential biomarkers for LUAD.MethodsTo assess the differentially methylation CpG sites of EGFR in LUAD, we used an integrative study of Illumina HumanMethylation450K and RNA-seq data from The Cancer Genome Atlas (TCGA). We evaluated and compared EGFR multiple-omics data to explore the role of CpG sites located in EGFR promoter regions and gene body regions and the association with transcripts, protein expression levels, mutations, and somatic copy number variation. We calculated the correlation coefficients between CpG sites of EGFR and immune infiltration fraction (by MCPcounter and ESTIMATE) and immune-related pathways in LUAD. Finally, we validated the differential methylation of clinically and prognostically relevant CpG sites using quantitative methylation-specific PCR (qMSP).ResultsWe found that the methylation level of many EGFR CpGs in the promoter region was negatively correlated with the transcription level, protein expression, and SCNV, while the methylation at the gene body region was positively correlated with these features. The methylation level of EGFR CpGs in the promoter region was positively correlated with the level of immune infiltration and IFN-γ signature, while the opposite was found for methylation of the gene body region. The qMSP results showed that cg02316066 had a high methylation level, while cg02166842 had a low methylation level in LUAD. There was a high degree of co-methylation between cg02316066 and cg03046247.ConclusionOur data indicate that EGFR is an epigenetic regulator in LUAD acting through DNA methylation. Our research provides a theoretical basis for the further detection of EGFR DNA methylation as a predictive biomarker for LUAD survival and immunotherapy.

scholarly journals Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease

2015 ◽  
Vol 5 (1) ◽  
pp. 64-73 ◽  
Author(s):  
Tomoyuki Nagata ◽  
Nobuyuki Kobayashi ◽  
Jumpei Ishii ◽  
Shunichiro Shinagawa ◽  
Ritsuko Nakayama ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Methylation Level ◽  
Clinical Presentation ◽  
Neuropsychological Test ◽  
Cpg Sites ◽  
The Brain ◽  
Normal Controls ◽  
Methylation Ratio

Background/Aims: In the present study, we examined whether DNA methylation of the brain-derived neurotrophic factor (BDNF) promoter is associated with the manifestation and clinical presentation of Alzheimer's disease (AD). Methods: Of 20 patients with AD and 20 age-matched normal controls (NCs), the DNA methylation of the BDNF promoter (measured using peripheral blood samples) was completely analyzed in 12 patients with AD and 6 NCs. The resulting methylation levels were compared statistically. Next, we investigated the correlation between the DNA methylation levels and the clinical presentation of AD. Results: The total methylation ratio (in %) of the 20 CpG sites was significantly higher in the AD patients (5.08 ± 5.52%) than in the NCs (2.09 ± 0.81%; p < 0.05). Of the 20 CpG sites, the methylation level at the CpG4 site was significantly higher in the AD subjects than in the NCs (p < 0.05). Moreover, the methylation level was significantly and negatively correlated with some neuropsychological test subscores (registration, recall, and prehension behavior scores; p < 0.05). Conclusion: These results suggest that the DNA methylation of the BDNF promoter may significantly influence the manifestation of AD and might be associated with its neurocognitive presentation.

Epigenome-wide association study identifies Behçet’s disease-associated methylation loci in Han Chinese

Rheumatology ◽  
2019 ◽  
Vol 58 (9) ◽  
pp. 1574-1584 ◽  
Author(s):  
Hongsong Yu ◽  
Liping Du ◽  
Shenglan Yi ◽  
Qingfeng Wang ◽  
Yunyun Zhu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Study ◽  
Mrna Expression ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Han Chinese ◽  
Healthy Controls ◽  
Behcet's Disease ◽  
Cpg Sites ◽  
Aberrant Dna Methylation

Abstract Objective The aetiology of Behçet’s disease (BD), known as a systemic vasculitis, is not completely understood. Increasing evidence suggests that aberrant DNA methylation may contribute to the pathogenesis of BD. The aim of this epigenome-wide association study was to identify BD-associated methylation loci in Han Chinese. Methods Genome-wide DNA methylation profiles were compared between 60 BD patients and 60 healthy controls using the Infinium Human Methylation 450 K Beadchip. BD-associated methylation loci were validated in 100 BD patients and 100 healthy controls by pyrosequencing. Gene expression and cytokine production was quantified by real-time PCR and ELISA. Results A total of 4332 differentially methylated CpG sites were associated with BD. Five differentially methylated CpG sites (cg03546163, cg25114611, cg20228731, cg23261343 and cg14290576) revealed a significant hypomethylation status across four different genes (FKBP5, FLJ43663, RUNX2 and NFIL3) and were validated by pyrosequencing. Validation results showed that the most significant locus was located in the 5’UTR of FKBP5 (cg03546163, P = 3.81E-13). Four CpG sites with an aberrant methylation status, including cg03546163, cg25114611, cg23261343 and cg14290576, may serve as a diagnostic marker for BD (area under the receiver operating curve curve = 83.95%, 95% CI 78.20, 89.70%). A significantly inverse correlation was found between the degree of methylation at cg03546163 as well as cg25114611 and FKBP5 mRNA expression. Treatment with a demethylation agent, 5-Aza-2’-deoxycytidine resulted in an increase of FKBP5 mRNA expression and a stimulated IL-1β production. Conclusion Our findings suggest that aberrant DNA methylation, independently of previously known genetic variants, plays a vital role in the pathogenesis of BD. Trial registration Chinese Clinical Trial Registry, chictr.org.cn, ChiCTR-CCC-12002184.

scholarly journals DNA methylation patterns of β-globin cluster in β-thalassemia patients

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiuqin Bao ◽  
Yangjin Zuo ◽  
Diyu Chen ◽  
Cunyou Zhao
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Methylation Level ◽  
Epigenetic Modification ◽  
Fetal Hemoglobin ◽  
Cpg Sites ◽  
Hbf Level ◽  
Globin Promoter ◽  
Methylation Patterns ◽  
Normal Controls

Abstract Background Reactivation of fetal hemoglobin (HbF, α2γ2) holds a therapeutic target for β-thalassemia and sickle cell disease. Although many HbF regulators have been identified, the methylation patterns in β-globin cluster driving the fetal-to-adult hemoglobin switch remains to be determined. Results Here, we evaluated DNA methylation patterns of the β-globin cluster from peripheral bloods of 105 β0/β0 thalassemia patients and 44 normal controls. We also recruited 15 bone marrows and 4 cord blood samples for further evaluation. We identified that the CpG sites in the locus control region (LCR) DNase I hypersensitive site 4 and 3 (HS4-3) regions, and γ- and β-globin promoters displayed hypomethylation in β0/β0-thalassemia patients, especially for the patients with high HbF level, as compared with normal controls. Furthermore, hypomethylations in most of CpG sites of the HS4-3 core regions were also observed in bone marrows (BM) of β0/β0-patients compared with normal controls; and methylation level of γ-globin promoter -50 and + 17 CpG sites showed lower methylation level in patients with high HbF level compared with those with low HbF level and a negative correlation with HbF level among β0-thalassemia patients. Finally, γ-globin promoter + 17 and + 50 CpG sites also displayed significant hypomethylation in cord blood (CB) tissues compared with BM tissues from normal controls. Conclusions Our findings revealed methylation patterns in β-globin cluster associated with β0 thalassemia disease and γ-globin expression, contributed to understand the epigenetic modification in β0 thalassemia patients and provided candidate targets for the therapies of β-hemoglobinopathies.

Sign in / Sign up

Export Citation Format

Share Document