scholarly journals Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution

2018 ◽  
Vol 45 (5) ◽  
pp. 1999-2008 ◽  
Author(s):  
Haiqiang Yao ◽  
Shanlan Mo ◽  
Ji Wang ◽  
Yingshuai Li ◽  
Chong-Zhi Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Metabolic Disorders ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Body Type ◽  
Peripheral Blood Mononuclear ◽  
Molecular Features ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Methylated Genes

Background/Aims: Metabolic diseases are leading health concerns in today’s global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. Methods: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs). Eight volunteers had PC and 4 had balanced constitutions. Results: Methylation data indicated a genome-scale hyper-methylation pattern in PC. We located 288 differentially methylated probes (DMPs). A total of 256 genes were mapped, and some of these were metabolic-related. SQSTM1, DLGAP2 and DAB1 indicated diabetes mellitus; HOXC4 and SMPD3, obesity; and GRWD1 and ATP10A, insulin resistance. According to Ingenuity Pathway Analysis (IPA), differentially methylated genes were abundant in multiple metabolic pathways. Conclusion: Our results suggest the potential risk for metabolic disorders in individuals with PC. We also explain the clinical characteristics of PC with DNA methylation features.

scholarly journals Genome-Wide Methylation Profiling in Canine Mammary Tumor Reveals miRNA Candidates Associated with Human Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1466
Author(s):  
Su-Jin Jeong ◽  
Kang-Hoon Lee ◽  
A-Reum Nam ◽  
Je-Yoel Cho
Keyword(s):  
Breast Cancer ◽  
Mammary Tumor ◽  
Mononuclear Cells ◽  
Aberrant Methylation ◽  
Canine Mammary Tumor ◽  
Promoter Regions ◽  
Peripheral Blood Mononuclear ◽  
Genome Wide ◽  
Differentially Methylated Genes ◽  
Methylation Profiling

Genome-wide methylation profiling is used in breast cancer (BC) studies, because DNA methylation is a crucial epigenetic regulator of gene expression, involved in many diseases including BC. We investigated genome-wide methylation profiles in both canine mammary tumor (CMT) tissues and peripheral blood mononuclear cells (PBMCs) using reduced representation bisulfite sequencing (RRBS) and found unique CMT-enriched methylation signatures. A total of 2.2–4.2 million cytosine–phosphate–guanine (CpG) sites were analyzed in both CMT tissues and PBMCs, which included 40,000 and 28,000 differentially methylated regions (DMRs) associated with 341 and 247 promoters of differentially methylated genes (DMGs) in CMT tissues and PBMCs, respectively. Genes related to apoptosis and ion transmembrane transport were hypermethylated, but cell proliferation and oncogene were hypomethylated in tumor tissues. Gene ontology analysis using DMGs in PBMCs revealed significant methylation changes in the subset of immune cells and host defense system-related genes, especially chemokine signaling pathway-related genes. Moreover, a number of CMT tissue-enriched DMRs were identified from the promoter regions of various microRNAs (miRNAs), including cfa-mir-96 and cfa-mir-149, which were reported as cancer-associated miRNAs in humans. We also identified novel miRNAs associated with CMT which can be candidates for new miRNAs associated with human BC. This study may provide new insight for a better understanding of aberrant methylation associated with both human BC and CMT, as well as possible targets for methylation-based BC diagnostic markers.

scholarly journals Integrated analysis of the methylome and transcriptome of chickens with fatty liver hemorrhagic syndrome

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaodong Tan ◽  
Ranran Liu ◽  
Yonghong Zhang ◽  
Xicai Wang ◽  
Jie Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Fatty Acid ◽  
Fatty Liver ◽  
Negative Relationship ◽  
Integrated Analysis ◽  
Pathway Enrichment Analysis ◽  
Gene Body ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Methylated Genes

Abstract Background DNA methylation, a biochemical modification of cytosine, has an important role in lipid metabolism. Fatty liver hemorrhagic syndrome (FLHS) is a serious disease and is tightly linked to lipid homeostasis. Herein, we compared the methylome and transcriptome of chickens with and without FLHS. Results We found genome-wide dysregulated DNA methylation pattern in which regions up- and down-stream of gene body were hypo-methylated in chickens with FLHS. A total of 4155 differentially methylated genes and 1389 differentially expressed genes were identified. Genes were focused when a negative relationship between mRNA expression and DNA methylation in promoter and gene body were detected. Based on pathway enrichment analysis, we found expression of genes related to lipogenesis and oxygenolysis (e.g., PPAR signaling pathway, fatty acid biosynthesis, and fatty acid elongation) to be up-regulated with associated down-regulated DNA methylation. In contrast, genes related to cellular junction and communication pathways (e.g., vascular smooth muscle contraction, phosphatidylinositol signaling system, and gap junction) were inhibited and with associated up-regulation of DNA methylation. Conclusions In the current study, we provide a genome-wide scale landscape of DNA methylation and gene expression. The hepatic hypo-methylation feature has been identified with FLHS chickens. By integrated analysis, the results strongly suggest that increased lipid accumulation and hepatocyte rupture are central pathways that are regulated by DNA methylation in chickens with FLHS.

scholarly journals Genome-Wide DNA Methylation Signatures Predict the Early Asymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6291
Author(s):  
Michael A. Bauer ◽  
Valentina K. Todorova ◽  
Annjanette Stone ◽  
Weleetka Carter ◽  
Matthew D. Plotkin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Mononuclear Cells ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Regulation Of Transcription ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Ventricular Ejection Fraction ◽  
Genome Wide

Chemotherapy with doxorubicin (DOX) may cause unpredictable cardiotoxicity. This study aimed to determine whether the methylation signature of peripheral blood mononuclear cells (PBMCs) prior to and after the first cycle of DOX-based chemotherapy could predict the risk of cardiotoxicity in breast cancer patients. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) by >10%. DNA methylation of PBMCs from 9 patients with abnormal LVEF and 10 patients with normal LVEF were examined using Infinium HumanMethylation450 BeadChip. We have identified 14,883 differentially methylated CpGs at baseline and 18,718 CpGs after the first cycle of chemotherapy, which significantly correlated with LVEF status. Significant differentially methylated regions (DMRs) were found in the promoter and the gene body of SLFN12, IRF6 and RNF39 in patients with abnormal LVEF. The pathway analysis found enrichment for regulation of transcription, mRNA splicing, pathways in cancer and ErbB2/4 signaling. The preliminary results from this study showed that the DNA methylation profile of PBMCs may predict the risk of DOX-induced cardiotoxicity prior to chemotherapy. Further studies with larger cohorts of patients are needed to confirm these findings.

scholarly journals Genome-Wide DNA Methylation Analysis of Soybean Curled-Cotyledons Mutant and Functional Evaluation of a Homeodomain-Leucine Zipper (HD-Zip) I Gene GmHDZ20

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Yang ◽  
Zhongyi Yang ◽  
Zhuozhuo Mao ◽  
Yali Li ◽  
Dezhou Hu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcription Factor ◽  
Leucine Zipper ◽  
Functional Study ◽  
Functional Evaluation ◽  
Whole Genome ◽  
Ontology Term ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Methylated Genes

DNA methylation is a major, conserved epigenetic modification that influences many biological processes. Cotyledons are specialized tissues that provide nutrition for seedlings at the early developmental stage. To investigate the patterns of genomic DNA methylation of germinated cotyledons in soybean (Glycine max) and its effect on cotyledon development, we performed a genome-wide comparative analysis of DNA methylation between the soybean curled-cotyledons (cco) mutant, which has abnormal cotyledons, and its corresponding wild type (WT) by whole-genome bisulfite sequencing. The cco mutant was methylated at more sites but at a slightly lower level overall than the WT on the whole-genome level. A total of 46 CG-, 92 CHG-, and 9723 CHH- (H = A, C, or T) differentially methylated genes (DMGs) were identified in cotyledons. Notably, hypomethylated CHH-DMGs were enriched in the gene ontology term “sequence-specific DNA binding transcription factor activity.” We selected a DMG encoding a homeodomain-leucine zipper (HD-Zip) I subgroup transcription factor (GmHDZ20) for further functional characterization. GmHDZ20 localized to the nucleus and was highly expressed in leaf and cotyledon tissues. Constitutive expression of GmHDZ20 in Arabidopsis thaliana led to serrated rosette leaves, shorter siliques, and reduced seed number per silique. A yeast two-hybrid assay revealed that GmHDZ20 physically interacted with three proteins associated with multiple aspects of plant growth. Collectively, our results provide a comprehensive study of soybean DNA methylation in normal and aberrant cotyledons, which will be useful for the identification of specific DMGs that participate in cotyledon development, and also provide a foundation for future in-depth functional study of GmHDZ20 in soybean.

Abstract 565: Genome-wide miRNA Expression Profiling and OPLS Discriminant Analysis in Hypertension and Cardiac Disease

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Maria João Pinho ◽  
Manuel Vaz-da-Silva ◽  
José M Cabral ◽  
Joana Afonso ◽  
Paula Serrão ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Cardiac Disease ◽  
Mononuclear Cells ◽  
Principal Component ◽  
Multidimensional Data ◽  
Peripheral Blood Mononuclear ◽  
Mirna Expression Pattern ◽  
Genome Wide ◽  
A Genome ◽  
And Control

MicroRNAs (miRNAs) are regulators of gene expression and play a key role in the pathophysiology of various disease processes, namely cardiovascular disease. This study aimed at the identification of the miRNA expression pattern of peripheral blood mononuclear cells derived from hypertensive subjects (HT) and non-hypertensive subjects with cardiac disease (CD) using a genome-wide approach. Furthermore, we explored the potential of orthogonal partial least squares-discrimination analysis (OPLS-DA) to analyze miRNA expression data. The homogeneity of the population was assessed with Principal Component Analysis (PCA) and verified by the clear separation of the three groups on the basis of the miRNA expression levels. Moreover, local PCA of HT group indicates the splitting of this group in two distinct subgroups. This distinction correlates with two subject’s characteristics (smoking habits and history of myocardial infarction) that are closest to the CD group. OPLS-DA analysis confirms the separation of three groups and identified the most important miRNA to discrimination between groups. Among the most influential miRNA to the positive differentiation of HT from CD and control, several of them are relevant to endothelial dysfunction. On the other hand, miRNAs associated with angiogenesis positively differentiate CD from HT and control. Mir-186, a regulator of myogenin, is the most important miRNA to discriminate HT from CD. These results provide evidence of altered miRNA profile in hypertensives and cardiac disease and demonstrate that PCA and OPLS-DA are very useful and robust tools to analyze how different miRNAs contribute to the separations of groups and to find interesting patterns within the multidimensional data.

scholarly journals POS0415 BLOOD-DERIVED DNA METHYLATION EPI-SIGNATURES ASSOCIATED WITH ANKYLOSING SPONDYLITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 437.3-437
Author(s):  
M. Xiao ◽  
J. Gu
Keyword(s):  
Dna Methylation ◽  
Ankylosing Spondylitis ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Sample Collection ◽  
Peripheral Blood Mononuclear ◽  
Staff Members ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Receptor Signaling Pathway

Background:Most (~90%) of the ankylosing spondylitis (AS) susceptibility loci are undefined and located in non-coding regions. Epigenetic changes may alter the expression of genes involved in AS and explain part of the missing heritability. 1Objectives:To identify novel DNA methylation sites significant for AS and comprehensively understand the underlying pathological mechanism.Methods:Genome-wide DNA methylation of blood samples from 30 AS patients and 15 health controls was measured on the Infinium® MethylationEPIC BeadChip microarray. Methylome data were analyzed with ChAMP package in R.Results:The epigenome-wide association analysis identified 4,794 differentially methylated positions (DMPs) (FDR <0.05 and delta β >0.05), including 3,294 (68.7%) hypermethylated and 1,500 (31.3%) hypomethylated positions in AS patients (Figure 1A). The identified DMPs allowed clear distinction of most AS cases from controls in the PCA (Figure 1B) and unsupervised hierarchical clustering (Figure 1C). KEGG pathway analysis of AS associated DMPs enriched in T cell receptor signaling pathway, Th1 and Th2 cell differentiation. Besides, a total of 1,048 differentially variable positions (DVPs) were identified, the majority of which (974, 92.9%) were hypervariable in AS, while only 74 DVPs were hypovariable. The increased DNA methylation variability in disease were in line with the previous observation in other diseases, indicating the intrinsic heterogeneity in AS patients, which might be influenced by diverse factors, such as disease activity and treatment.Figure 1.Conclusion:Peripheral blood mononuclear cells from AS patients display aberrant DNA methylome and increased DNA methylation variability. The results enhanced our understanding of the important role of DNA methylation in pathology of AS and offered the possibility of identifying new targets for intervention.References:[1]Whyte JM, Ellis JJ, Brown MA, et al. Best practices in DNA methylation: lessons from inflammatory bowel disease, psoriasis and ankylosing spondylitis. Arthritis Res Ther 2019; 21:133.Acknowledgements:We appreciate all the staff members of the department of rheumatology of the Third Affiliated Hospital of Sun Yat-sen University for assistance and support in the patient’s recruitment and sample collection.Disclosure of Interests:None declared

scholarly journals Mild SARS-CoV-2 infection modifies DNA methylation of peripheral blood mononuclear cells from COVID-19 convalescents

2021 ◽  
Author(s):  
Johanna Huoman ◽  
Shumaila Sayyab ◽  
Eirini Apostolou ◽  
Lovisa Karlsson ◽  
Lucas Porcile ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Network Analyses ◽  
Differentially Methylated Genes ◽  
Blood Mononuclear Cells ◽  
Methylation Patterns

Background: Coronaviruses such as SARS-CoV-2 may circumvent host defence mechanisms by hijacking host proteins, possibly by altering DNA methylation patterns in host cells. While most epigenetic studies have been performed in severely ill COVID-19 patients, studies on individuals who have recovered from mild-to-moderate disease remain scarce. The aim of this study was to assess epigenome-wide DNA methylation patterns in COVID-19 convalescents compared to uninfected controls from before and after the pandemic outbreak began. Methods: DNA was extracted from peripheral blood mononuclear cells originating from uninfected controls before (Pre20, n=5) and after (Con, n=18) 2020, COVID-19 convalescents (CC19, n=14) and symptom-free individuals with a SARS-CoV-2-specific T cell response (SFT, n=6), as well as from Pre20 (n=4) samples stimulated in vitro with SARS-CoV-2. Subsequently, epigenome-wide DNA methylation analyses were performed using the Illumina MethylationEPIC 850K array, and statistical and bioinformatic analyses comprised differential DNA methylation, pathway over-representation and module identification network analyses. Results: DNA methylation patterns of COVID-19 convalescents were altered as compared to uninfected controls, with similar results observed in in vitro stimulations of PBMC with SARS-CoV-2. Differentially methylated genes from the in vivo comparison constituted the foundation for the identification of a possibly SARS-CoV-2-induced module, containing 66 genes of which six could also be identified in corresponding analyses of the in vitro data (TP53, INS, HSPA4, SP1, ESR1 and FAS). Pathway over-representation analyses revealed involvement of Wnt, cadherin and apoptosis signalling pathways amongst others. Furthermore, numerous interactions were found between the obtained differentially methylated genes from both settings and the network analyses when overlaying the data unto the SARS-CoV-2 interactome. Conclusions: Epigenome-wide DNA methylation patterns of individuals that have recovered from mild-to-moderate COVID-19 are different from those of non-infected controls. The observed alterations during both in vivo and in vitro exposure to SARS-CoV-2 showed involvement in interactions and pathways that are highly relevant to COVID-19. The present study provides indications that DNA methylation is one of several epigenetic mechanisms that is altered upon SARS-CoV-2 infection. Further studies on the mechanistic underpinnings should determine whether the observed effects are reflecting host-protective antiviral defence or targeted viral hijacking to evade host defence.

scholarly journals DNA methylome profiling reveals epigenetic regulation of lipoprotein-associated phospholipase A2 in human vulnerable atherosclerotic plaque

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jingjin Li ◽  
Xiaoping Zhang ◽  
Mengxi Yang ◽  
Hang Yang ◽  
Ning Xu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Atherosclerotic Plaque ◽  
Epigenetic Regulation ◽  
Cpg Islands ◽  
Integrated Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Promoter Regions ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Methylated Genes

Abstract Background Atherosclerotic plaque vulnerability is a key feature of atheroprogression and precipitating acute cardiovascular events. Although the pivotal role of epigenetic regulation in atherosclerotic plaque destabilization is being recognized, the DNA methylation profile and its potential role in driving the progression and destabilization of atherosclerotic cardiovascular disease remains largely unknown. We conducted a genome-wide analysis to identify differentially methylated genes in vulnerable and non-vulnerable atherosclerotic lesions to understand more about pathogenesis. Results We compared genome-wide DNA methylation profiling between carotid artery plaques of patients with clinically symptomatic (recent stroke or transient ischemic attack) and asymptomatic disease (no recent stroke) using Infinium Methylation BeadChip arrays, which revealed 90,368 differentially methylated sites (FDR < 0.05, |delta beta|> 0.03) corresponding to 14,657 annotated genes. Among these genomic sites, 30% were located at the promoter regions and 14% in the CpG islands, according to genomic loci and genomic proximity to the CpG islands, respectively. Moreover, 67% displayed hypomethylation in symptomatic plaques, and the differentially hypomethylated genes were found to be involved in various aspects of inflammation. Subsequently, we focus on CpG islands and revealed 14,596 differentially methylated sites (|delta beta|> 0.1) located at the promoter regions of 7048 genes. Integrated analysis of methylation and gene expression profiles identified that 107 genes were hypomethylated in symptomatic plaques and showed elevated expression levels in both advanced plaques and ruptured plaques. The imprinted gene PLA2G7, which encodes lipoprotein-associated phospholipase A2 (Lp-PLA2), was one of the top hypomethylated genes with an increased expression upon inflammation. Further, the hypomethylated CpG site at the promoter region of PLA2G7 was identified as cg11874627, demethylation of which led to increased binding of Sp3 and expression of Lp-PLA2 through bisulfate sequencing, chromatin immunoprecipitation assay and enzyme-linked immunosorbent assay. These effects were further enhanced by deacetylase. Conclusion Extensive DNA methylation modifications serve as a new and critical layer of biological regulation that contributes to atheroprogression and destabilization via inflammatory processes. Revelation of this hitherto unknown epigenetic regulatory mechanism could rejuvenate the prospects of Lp-PLA2 as a therapeutic target to stabilize the atherosclerotic plaque and reduce clinical sequelae.

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