Chromatin, DNA Methylation, RNAi and Epigenetic Regulation

2009 ◽  
pp. 441-458
Author(s):  
Shawn Kaeppler
Keyword(s):  
Dna Methylation ◽  
Epigenetic Regulation

scholarly journals Altered DNA methylation pattern reveals epigenetic regulation of Hox genes in thoracic aortic dissection and serves as a biomarker in disease diagnosis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Peiru Liu ◽  
Jing Zhang ◽  
Duo Du ◽  
Dandan Zhang ◽  
Zelin Jin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Aortic Dissection ◽  
Epigenetic Regulation ◽  
Heart Development ◽  
Type A ◽  
Methylation Pattern ◽  
Healthy Controls ◽  
Global Methylation ◽  
Thoracic Aortic Dissection

Abstract Background Thoracic aortic dissection (TAD) is a severe disease with limited understandings in its pathogenesis. Altered DNA methylation has been revealed to be involved in many diseases etiology. Few studies have examined the role of DNA methylation in the development of TAD. This study explored alterations of the DNA methylation landscape in TAD and examined the potential role of cell-free DNA (cfDNA) methylation as a biomarker in TAD diagnosis. Results Ascending aortic tissues from TAD patients (Stanford type A; n = 6) and healthy controls (n = 6) were first examined via whole-genome bisulfite sequencing (WGBS). While no obvious global methylation shift was observed, numerous differentially methylated regions (DMRs) were identified, with associated genes enriched in the areas of vasculature and heart development. We further confirmed the methylation and expression changes in homeobox (Hox) clusters with 10 independent samples using bisulfite pyrosequencing and quantitative real-time PCR (qPCR). Among these, HOXA5, HOXB6 and HOXC6 were significantly down-regulated in TAD samples relative to controls. To evaluate cfDNA methylation pattern as a biomarker in TAD diagnosis, cfDNA from TAD patients (Stanford type A; n = 7) and healthy controls (n = 4) were examined by WGBS. A prediction model was built using DMRs identified previously from aortic tissues on methylation data from cfDNA. Both high sensitivity (86%) and specificity (75%) were achieved in patient classification (AUC = 0.96). Conclusions These findings showed an altered epigenetic regulation in TAD patients. This altered epigenetic regulation and subsequent altered expression of genes associated with vasculature and heart development, such as Hox family genes, may contribute to the loss of aortic integrity and TAD pathogenesis. Additionally, the cfDNA methylation in TAD was highly disease specific, which can be used as a non-invasive biomarker for disease prediction.

scholarly journals Whole-Blood Methylation Analysis Reveals Respiratory Environmental Functional Pathways Involved in Severity Following SARS-CoV-2 Infection

2021 ◽  
Author(s):  
Guillermo Barturen ◽  
Elena Carnero-Montoro ◽  
Manuel Martínez-Bueno ◽  
Silvia Rojo-Rello ◽  
Beatriz Sobrino ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Epigenetic Regulation ◽  
Strong Relationship ◽  
Autoimmune Disorder ◽  
Methylation Analysis ◽  
Functional Pathways ◽  
Interferon Responses ◽  
Inflammatory Syndrome ◽  
Dna Genotyping

SARS-CoV-2 causes a severe inflammatory syndrome called COVID-19 that primarily affects the lungs leading, in many cases, to bilateral pneumonia, severe dyspnea and in ~5% of the cases, death. The mechanisms through which this occurs are still being elucidated. A strong relationship between COVID-19 progression and autoimmune disorder pathogenesis has been identified as an exacerbated interferon immune response or an inflammatory condition mediated by an increase of pro-inflammatory cytokine production, among other. DNA methylation is known to regulate immune response processes, thus COVID-19 progression might be also conditioned by DNA methylation changes not studied in depth, yet. Thus, here an epigenome-wide DNA methylation analysis combined with DNA genotyping for 101 and 473 SARS-CoV-2 negative and positive lab tested individuals, respectively, from two different clinical centers is presented in order to evaluate the implications of the epigenetic regulation in the course of COVID-19 disease. The results reveal the existence of an epigenome regulation of functional pathways associated with the COVID-19 progression, such as innate interferon responses, hyperactivation of B and T lymphocytes, phagocytosis and innate C-type lectin DC-SIGN. These DNA methylation changes were found to be regulated by genetic loci associated with COVID-19 susceptibility and autoimmune disease. In mild COVID-19 patients hypomethylation of CpGs regulating genes within the AKT signaling pathway, and the hypermethylation of a group of CpGs related to environmental traits regulating IL-6 expression via the transcription factor CEBP, discriminate these individuals from those who develop the most critical outcomes of the disease. Thus, the analysis points out to an environmental contribution that mediated by DNA methylation changes in SARS-CoV-2 positive patients, might be playing a role in triggering the cytokine storm described in the most severe cases. In addition, important differences were found in terms of epigenetic regulation between severe and mild cases when compared with systemic autoimmune diseases.

scholarly journals Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiaolian Gu ◽  
Linda Boldrup ◽  
Philip J. Coates ◽  
Robin Fahraeus ◽  
Elisabet Nylander ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Regulation ◽  
Cpg Sites ◽  
Disease Specific

Regulation of adenosine A2Areceptor gene expression in a model of binge eating in the amygdaloid complex of female rats

2019 ◽  
Vol 33 (12) ◽  
pp. 1550-1561 ◽  
Author(s):  
Maria Vittoria Micioni Di Bonaventura ◽  
Mariangela Pucci ◽  
Maria Elena Giusepponi ◽  
Adele Romano ◽  
Catia Lambertucci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Binge Eating ◽  
Epigenetic Regulation ◽  
Methylation Status ◽  
Amygdaloid Complex ◽  
Female Rats ◽  
Control Group ◽  
Compensatory Mechanism ◽  
Mrna Levels

Background:Pharmacological treatment approaches for eating disorders, such as binge eating disorder and bulimia nervosa, are currently limited.Methods and aims:Using a well-characterized animal model of binge eating, we investigated the epigenetic regulation of the A2AAdenosine Receptor (A2AAR) and dopaminergic D2 receptor (D2R) genes.Results:Gene expression analysis revealed a selective increase of both receptor mRNAs in the amygdaloid complex of stressed and restricted rats, which exhibited binge-like eating, when compared to non-stressed and non-restricted rats. Consistently, pyrosequencing analysis revealed a significant reduction of the percentage of DNA methylation but only at the A2AAR promoter region in rats showing binge-like behaviour compared to the control animals. Focusing thus on A2AAR agonist (VT 7) administration (which inhibited the episode of binge systemically at 0.1 mg/kg or intra-central amygdala (CeA) injection at 900 ng/side) induced a significant increase of A2AAR mRNA levels in restricted and stressed rats when compared to the control group. In addition, we observed a significant decrease in A2AAR mRNA levels in rats treated with the A2AAR antagonist (ANR 94) at 1 mg/kg. Consistent changes in the DNA methylation status of the A2AAR promoter were found in restricted and stressed rats after administration of VT 7 or ANR 94.Conclusion:We confirm the role of A2AAR in binge eating behaviours, and we underline the importance of epigenetic regulation of the A2AAR gene, possibly due to a compensatory mechanism to counteract the effect of binge eating. We suggest that A2AAR activation, inducing receptor gene up-regulation, could be relevant to reduction of food consumption.

scholarly journals Identification of bovine CpG SNPs as potential targets for epigenetic regulation via DNA methylation

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222329 ◽  
Author(s):  
Mariângela B. C. Maldonado ◽  
Nelson B. de Rezende Neto ◽  
Sheila T. Nagamatsu ◽  
Marcelo F. Carazzolle ◽  
Jesse L. Hoff ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Regulation

scholarly journals Epigenetic regulation (DNA methylation, histone modifications) of the 11p15 mucin genes (MUC2, MUC5AC, MUC5B, MUC6) in epithelial cancer cells

Oncogene ◽  
2007 ◽  
Vol 26 (45) ◽  
pp. 6566-6576 ◽  
Author(s):  
A Vincent ◽  
M Perrais ◽  
J-L Desseyn ◽  
J-P Aubert ◽  
P Pigny ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cancer Cells ◽  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Epithelial Cancer ◽  
Mucin Genes

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.

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