scholarly journals Genome‑wide profiling of DNA methylation and gene expression unravel the epigenetic landscape in diabetes-related hypothyroidism

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jingyi Luo ◽  
Xiaoxia Wang ◽  
Li Yuan ◽  
Lixin Guo
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Rna Sequencing ◽  
High Glucose ◽  
Epigenetic Modification ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Normal Medium ◽  
Genome Wide ◽  
Low T3

Abstract Background Type 2 diabetes mellitus (T2DM) and hypothyroidism are two common endocrine diseases and the phenomenon that the prevalence of diabetes-related hypothyroidism shows a significant upward trend deserves further attention, but the specific pathogenesis is not yet clear. The study aimed to explore the molecular mechanisms on DNA methylation regulating gene expression and participating in diabetes-related hypothyroidism through genome-wide DNA methylation and RNA sequencing. Results The prevalence of hypothyroidism in T2DM patients was significantly higher than that in patients without T2DM (P = 0.018). Meanwhile, high TSH and low T3 and T4 levels were detected in diabetic mice. Low T3 and T4 levels were detected in Nthy-ori3-1 cells incubated in high-glucose medium. Differentially expressed genes (DEGs) and differentially methylated regions (DMRs) were detected by RNA sequencing and reduced representation bisulfite sequencing in Nthy-ori3-1 cells cultured in high-glucose and normal medium. Functional enrichment analyses reveled that DMRs and DEGs were related to significant pathways including Ras, Wnt and MAPK pathways. Conclusions We observed the potential connection between T2DM and hypothyroidism. This study was the first one carrying out DNA methylation and gene expression profiles to explore epigenetic modification in diabetes-related hypothyroidism, which provided information for the detailed study of the molecular mechanism in diabetes-related hypothyroidism.

scholarly journals Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Shasha Su ◽  
Wenjie Kong ◽  
Jing Zhang ◽  
Xinguo Wang ◽  
Hongmei Guo
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Dna Methylation ◽  
Expression Profiles ◽  
Osteoclast Differentiation ◽  
Functional Enrichment ◽  
Functional Network ◽  
Integrated Analysis ◽  
Genome Wide ◽  
Potential Biomarker

Abstract Ulcerative colitis (UC) is a prevalent relapsing-remitting inflammatory bowel disease whose pathogenetic mechanisms remain elusive. In the present study, colonic biopsies samples from three UC patients treated in the Traditional Chinese Medicine Hospital and three healthy controls were obtained. The genome-wide mRNA and lncRNA expression of the samples were profiled through Agilent gene expression microarray. Moreover, the genome-wide DNA methylation dataset of normal and UC colon tissues was also downloaded from GEO for a collaborative analysis. Differential expression of lncRNA (DELs) and mRNAs (DEMs) in UC samples compared with healthy samples were identified by using limma Bioconductor package. Differentially methylated promoters (DMPs) in UC samples compared with controls were obtained through comparing the average methylation level of CpGs located at promoters by using t-test. Functional enrichment analysis was performed by the DAVID. STRING database was applied to the construction of gene functional interaction network. As a result, 2090 DEMs and 1242 DELs were screened out in UC samples that were closely associated with processes related to complement and coagulation cascades, osteoclast differentiation vaccinia, and hemorrhagic diseases. A total of 90 DEMs and 72 DELs were retained for the construction of functional network for the promoters of their corresponding genes were identified as DMPs. S100A9, HECW2, SOD3 and HIX0114733 showed high interaction degrees in the functional network, and expression of S100A9 was confirmed to be significantly elevated in colon tissues of UC patients compared with that of controls by qRT-PCR that was consistent with gene microarray analysis. These indicate that S100A9 could potentially be used as predictive biomarkers in UC.

scholarly journals Monozygotic Twins Discordant for Immunoglobulin A Nephropathy Display Differences in DNA Methylation and Gene Expression

2020 ◽  
pp. 1-10
Author(s):  
Min Wei ◽  
Sijun Meng ◽  
Sufang Shi ◽  
Lijun Liu ◽  
Xujie Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Profiles ◽  
Immunoglobulin A ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Genome Wide ◽  
Mz Twins

<b><i>Introduction:</i></b> Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. It involves both genetic and environmental factors, among which DNA methylation, the most studied epigenetic modification, was shown to play a role. Here, we assessed genome-wide DNA methylation and gene expression profiles in 2 pairs of IgAN-discordant monozygotic (MZ) twins, in order to characterize methylation changes and their potential influences on gene expression in IgAN. <b><i>Methods:</i></b> Genome-wide DNA methylation and gene expression profiles were evaluated in peripheral blood mononuclear cells obtained from 2 IgAN-discordant MZ twins. Differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were detected, and an integrated analysis was performed. Finally, functional enrichment analysis was done for DMR-associated genes and DEGs. <b><i>Results:</i></b> Totally 521 DMRs were detected for 2 IgAN-discordant MZ twins. Among them, 9 DMRs were found to be mapped to genes that differentially expressed in 2 MZ twins, indicating the potential regulatory mechanisms of expression for these 9 genes (<i>MNDA</i>, <i>DYSF</i>, <i>IL1R2</i>, <i>TLR6</i>, <i>TREML2</i>, <i>TREM1</i>, <i>IL32</i>, <i>S1PR5</i>, and <i>ADGRE3</i>) in IgAN. Biological process analysis of them showed that they were mostly involved in the immune system process. Functional enrichment analysis of DEGs and DMR-associated genes both identified multiple pathways relevant to inflammatory and immune responses. And DMR-associated genes were significantly enriched in terms related to T-cell function. <b><i>Conclusions:</i></b> Our findings indicate that changes in DNA methylation patterns were involved in the pathogenesis of IgAN. Nine target genes detected in our study may provide new ideas for the exploration of molecular mechanisms of IgAN.

scholarly journals Genome-Wide DNA Methylation Profiling in the Lotus (Nelumbo nucifera) Flower Showing its Contribution to the Stamen Petaloid

Plants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 135 ◽  
Author(s):  
Zhongyuan Lin ◽  
Meihui Liu ◽  
Rebecca Njeri Damaris ◽  
Tonny Maraga Nyong’a ◽  
Dingding Cao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Epigenetic Modification ◽  
Nelumbo Nucifera ◽  
Flower Formation ◽  
Relationship Analysis ◽  
Genome Wide ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

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.

scholarly journals DNA hypermethylation associated with upregulated gene expression in prostate cancer demonstrates the diversity of epigenetic regulation

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Ieva Rauluseviciute ◽  
Finn Drabløs ◽  
Morten Beck Rye
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Dna Methylation ◽  
Epigenetic Regulation ◽  
Normal Tissue ◽  
Expression Profiles ◽  
Expression Data ◽  
Dna Hypermethylation ◽  
Genome Wide ◽  
A Genome

Abstract Background Prostate cancer (PCa) has the highest incidence rates of cancers in men in western countries. Unlike several other types of cancer, PCa has few genetic drivers, which has led researchers to look for additional epigenetic and transcriptomic contributors to PCa development and progression. Especially datasets on DNA methylation, the most commonly studied epigenetic marker, have recently been measured and analysed in several PCa patient cohorts. DNA methylation is most commonly associated with downregulation of gene expression. However, positive associations of DNA methylation to gene expression have also been reported, suggesting a more diverse mechanism of epigenetic regulation. Such additional complexity could have important implications for understanding prostate cancer development but has not been studied at a genome-wide scale. Results In this study, we have compared three sets of genome-wide single-site DNA methylation data from 870 PCa and normal tissue samples with multi-cohort gene expression data from 1117 samples, including 532 samples where DNA methylation and gene expression have been measured on the exact same samples. Genes were classified according to their corresponding methylation and expression profiles. A large group of hypermethylated genes was robustly associated with increased gene expression (UPUP group) in all three methylation datasets. These genes demonstrated distinct patterns of correlation between DNA methylation and gene expression compared to the genes showing the canonical negative association between methylation and expression (UPDOWN group). This indicates a more diversified role of DNA methylation in regulating gene expression than previously appreciated. Moreover, UPUP and UPDOWN genes were associated with different compartments — UPUP genes were related to the structures in nucleus, while UPDOWN genes were linked to extracellular features. Conclusion We identified a robust association between hypermethylation and upregulation of gene expression when comparing samples from prostate cancer and normal tissue. These results challenge the classical view where DNA methylation is always associated with suppression of gene expression, which underlines the importance of considering corresponding expression data when assessing the downstream regulatory effect of DNA methylation.

scholarly journals Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheng Zhang ◽  
Bingye Zhang ◽  
Di Meng ◽  
Chunlin Ge
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Ppi Networks ◽  
Differentially Methylated Genes ◽  
Tumorigenesis And Progression

Abstract Background The incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis. Methods The gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein–protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database. Results We identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA. Conclusions Our study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.

OS11.5.A PATZ1 fusions define a novel molecularly distinct CNS tumor entity with a broad histological spectrum

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii14-ii15
Author(s):  
K T Al Halabi ◽  
P Sievers ◽  
D Stichel ◽  
A C Sommerkamp ◽  
M Sill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Rna Sequencing ◽  
Copy Number ◽  
Cns Tumors ◽  
Who Grade ◽  
Cns Tumor ◽  
Genome Wide ◽  
Tumor Entity ◽  
Reference Cohort

Abstract BACKGROUND DNA methylation profiling has emerged as a useful tool for robust classification of rare CNS tumors with a broad morphological spectrum. Routine diagnostic molecular profiling performed in Heidelberg and at international collaborating centers revealed a small but recurring number of CNS tumors with fusions of the PATZ1 gene coupled to either MN1 or EWSR1, displaying a distinct genome-wide methylation profile; indicating that these tumors could form a seperate biological entity. MATERIAL AND METHODS We obtained genome-wide DNA-methylation array profiling of 68 primary CNS tumors. RNA-sequencing was perfomed on (n=23/68, 34%) of the tumor samples, including (n=6) from fresh frozen tissue used for gene expression profiling. For n=3 cases, whole exome sequencing (WES) data was generated, and gene panel sequencing data was available for n=13 cases, We systematically reevaluated the histopahthological features of 14 tumors, while immunohistochemical (IHC) staining with Ki-67, GFAP, MAP2, NeuN, Olig-2, Synaptophysin, S-100 and Vimentin was performed for (n=12) tumors. We finally collected clinical data to preliminarily characterize this novel tumor entity. RESULTS A selected analysis of the tumors in this novel cohort (n=68), compared with a reference cohort consisting of 15 other low- and high-grade glial and glioneuronal tumor classes, confirmed a clearly distinct grouping. No similarity was seen with the MN1:BEND2 and MN1:CXXC5-fused CNS-tumors. Analysis of Copy number profiles derived from the DNA-methylation data showed a mostly quite genome, with (n=64/65, 98%) of tumors showing copy number variations on Chromosome 22. RNA-sequencing detected PATZ1 fusions in all tumors sequenced (n=12; MN1:PATZ1, n=11; EWSR1:PATZ1). IGF2, PAX2 and GATA2, all genes involved in brain stem cell biology, were upregulated compared to a combined reference cohort of other glioma subtypes. DNA-sequencing showed no relevant alterations at the level of point mutations or small insertions/deletions. The tumors in our cohort showed polyphenotypic histologies along the glial spectrum, with a subset of tumors being diagnosed as Gliobastoma, WHO Grade 4 and bi- and multiphasic differentaion patterns being evident. IHC performed on tissue available did not favor a particular lineage, with most tumors showing immunopositivity to GFAP. Reverse translation of the gene expression data showed a potential role for NG2 as immunostaining marker. The median age was 11.0 years (0–80), (MN1:PATZ1 manifested at a younger age (median = 4 years) vs EWSR1:PATZ1 (median = 14 years)). Median PFS was 12 months. CONCLUSION We describe here a novel, molecularly distinct CNS tumor class with strikingly variable histopathologic morphology. We postulate that the PATZ1 fusions are a key driver of tumor initiation. Preliminary indications suggest an intermediate prognosis.

Genome-wide Differential-based Analysis of the Relationship between DNA Methylation and Gene Expression in Cancer

2019 ◽  
Vol 14 (8) ◽  
pp. 783-792 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Chuanhua Kou ◽  
Shudong Wang ◽  
Yulin Zhang
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epigenetic Modification ◽  
Epigenetic Mechanism ◽  
Gene Body ◽  
Differential Analysis ◽  
Promoter Regions ◽  
Genome Wide ◽  
Significant Difference ◽  
The Relationship

Background:: DNA methylation is an epigenetic modification that plays an important role in regulating gene expression. There is evidence that the hypermethylation of promoter regions always causes gene silencing. However, how the methylation patterns of other regions in the genome, such as gene body and 3’UTR, affect gene expression is unknown. Objective:: The study aimed to fully explore the relationship between DNA methylation and expression throughout the genome-wide analysis which is important in understanding the function of DNA methylation essentially. Method:: In this paper, we develop a heuristic framework to analyze the relationship between the methylated change in different regions and that of the corresponding gene expression based on differential analysis. Results:: To understande the methylated function of different genomic regions, a gene is divided into seven functional regions. By applying the method in five cancer datasets from the Synapse database, it was found that methylated regions with a significant difference between cases and controls were almost uniformly distributed in the seven regions of the genome. Also, the effect of DNA methylation in different regions on gene expression was different. For example, there was a higher percentage of positive relationships in 1stExon, gene body and 3’UTR than in TSS1500 and TSS200. The functional analysis of genes with a significant positive and negative correlation between DNA methylation and gene expression demonstrated the epigenetic mechanism of cancerassociated genes. Conclusion:: Differential based analysis helps us to recognize the change in DNA methylation and how this change affects the change in gene expression. It provides a basis for further integrating gene expression and DNA methylation data to identify disease-associated biomarkers.

scholarly journals DNA Methylation of Enhancer Elements in Myeloid Neoplasms: Think Outside the Promoters?

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1424 ◽  
Author(s):  
Ordoñez ◽  
Martínez-Calle ◽  
Agirre ◽  
Prosper
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epigenetic Modification ◽  
Myeloproliferative Neoplasms ◽  
Regulation Of Gene Expression ◽  
Fine Tuning ◽  
Specific Gene ◽  
Gene Promoters ◽  
Regulatory Regions ◽  
Genome Wide

Gene regulation through DNA methylation is a well described phenomenon that has a prominent role in physiological and pathological cell-states. This epigenetic modification is usually grouped in regions denominated CpG islands, which frequently co-localize with gene promoters, silencing the transcription of those genes. Recent genome-wide DNA methylation studies have challenged this paradigm, demonstrating that DNA methylation of regulatory regions outside promoters is able to influence cell-type specific gene expression programs under physiologic or pathologic conditions. Coupling genome-wide DNA methylation assays with histone mark annotation has allowed for the identification of specific epigenomic changes that affect enhancer regulatory regions, revealing an additional layer of complexity to the epigenetic regulation of gene expression. In this review, we summarize the novel evidence for the molecular and biological regulation of DNA methylation in enhancer regions and the dynamism of these changes contributing to the fine-tuning of gene expression. We also analyze the contribution of enhancer DNA methylation on the expression of relevant genes in acute myeloid leukemia and chronic myeloproliferative neoplasms. The characterization of the aberrant enhancer DNA methylation provides not only a novel pathogenic mechanism for different tumors but also highlights novel potential therapeutic targets for myeloid derived neoplasms.

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