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 Crosstalk of DNA Methylation Triggered by Pathogen in Poplars With Different Resistances

2021 ◽  
Vol 12 ◽  
Author(s):  
Dandan Xiao ◽  
Ke Zhou ◽  
Xiaoqian Yang ◽  
Yuzhang Yang ◽  
Yudie Ma ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Epigenetic Regulation ◽  
Expression Profiles ◽  
Critical Role ◽  
Infection Process ◽  
Regulation Mechanism ◽  
Post Inoculation ◽  
Pathogen Infection ◽  
Methylation Ratio

DNA methylation plays crucial roles in responses to environmental stimuli. Modification of DNA methylation during development and abiotic stress responses has been confirmed in increasing numbers of plants, mainly annual plants. However, the epigenetic regulation mechanism underlying the immune response to pathogens remains largely unknown in plants, especially trees. To investigate whether DNA methylation is involved in the response to infection process or is related to the resistance differences among poplars, we performed comprehensive whole-genome bisulfite sequencing of the infected stem of the susceptible type Populus × euramerican ‘74/76’ and resistant type Populus tomentosa ‘henan’ upon Lonsdalea populi infection. The results revealed that DNA methylation changed dynamically in poplars during the infection process with a remarkable decrease seen in the DNA methylation ratio. Intriguingly, the resistant P. tomentosa ‘henan’ had a much lower basal DNA methylation ratio than the susceptible P. × euramerican ‘74/76’. Compared to mock-inoculation, both poplar types underwent post-inoculation CHH hypomethylation; however, significant decreases in mC and mCHH proportions were found in resistant poplar. In addition, most differentially CHH-hypomethylated regions were distributed in repeat and promoter regions. Based on comparison of DNA methylation modification with the expression profiles of genes, DNA methylation occurred in resistance genes, pathogenesis-related genes, and phytohormone genes in poplars during pathogen infection. Additionally, transcript levels of genes encoding methylation-related enzymes changed during pathogen infection. Interestingly, small-regulator miRNAs were subject to DNA methylation in poplars experiencing pathogen infection. This investigation highlights the critical role of DNA methylation in the poplar immune response to pathogen infection and provides new insights into epigenetic regulation in perennial plants in response to biotic stress.

Abstract LB-173: DNA methylation analysis reveals epigenetic regulation of neural differentiation in AT/RTs

2020 ◽  
Author(s):  
Kirsi Johanna Granberg ◽  
Joonas Tuominen ◽  
Kristiina Nordfors ◽  
Meeri Pekkarinen ◽  
Ville Kytölä ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Regulation ◽  
Neural Differentiation ◽  
Methylation Analysis ◽  
Dna Methylation Analysis

scholarly journals Gliadin Sequestration as a Novel Therapy for Celiac Disease: A Prospective Application for Polyphenols

2021 ◽  
Vol 22 (2) ◽  
pp. 595
Author(s):  
Charlene B. Van Buiten ◽  
Ryan J. Elias
Keyword(s):  
Immune Response ◽  
Celiac Disease ◽  
Gastrointestinal Symptoms ◽  
Autoimmune Disorder ◽  
Treatment Method ◽  
Mucosal Damage ◽  
Protective Effects ◽  
Novel Therapy ◽  
Gluten Proteins ◽  
Prospective Application

Celiac disease is an autoimmune disorder characterized by a heightened immune response to gluten proteins in the diet, leading to gastrointestinal symptoms and mucosal damage localized to the small intestine. Despite its prevalence, the only treatment currently available for celiac disease is complete avoidance of gluten proteins in the diet. Ongoing clinical trials have focused on targeting the immune response or gluten proteins through methods such as immunosuppression, enhanced protein degradation and protein sequestration. Recent studies suggest that polyphenols may elicit protective effects within the celiac disease milieu by disrupting the enzymatic hydrolysis of gluten proteins, sequestering gluten proteins from recognition by critical receptors in pathogenesis and exerting anti-inflammatory effects on the system as a whole. This review highlights mechanisms by which polyphenols can protect against celiac disease, takes a critical look at recent works and outlines future applications for this potential treatment method.

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 P46.03 DNA Methylation Analysis in Smokers and Non-Smokers (Passive and ex-Smokers)

2021 ◽  
Vol 16 (3) ◽  
pp. S490
Author(s):  
D.M. Aguilar-Beltrán ◽  
A.G. Alcázar-Ramos ◽  
A.L. Vega-Rodríguez ◽  
D.G. García-Gutiérrez ◽  
A.D. Bertadillo-Jilote ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Analysis ◽  
Dna Methylation Analysis
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