scholarly journals DNA Methylation As an Epigenetic Mechanism in the Development of Multiple Sclerosis

Acta Naturae ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 45-57
Author(s):  
Ivan S. Kiselev ◽  
Olga G. Kulakova ◽  
Aleksey N. Boyko ◽  
Olga O. Favorova
Keyword(s):  
Multiple Sclerosis ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Epigenetic Mechanism ◽  
Candidate Gene Approach ◽  
Published Data ◽  
Epigenetic Mechanisms ◽  
Cpg Dinucleotides ◽  
Methylation Of Dna

The epigenetic mechanisms of gene expression regulation are a group of the key cellular and molecular pathways that lead to inherited alterations in genes activity without changing their coding sequence. DNA methylation at the C5 position of cytosine in CpG dinucleotides is amongst the central epigenetic mechanisms. Currently, the number of studies that are devoted to the identification of methylation patterns specific to multiple sclerosis (MS), a severe chronic autoimmune disease of the central nervous system, is on a rapid rise. However, the issue of the contribution of DNA methylation to the development of the different clinical phenotypes of this highly heterogeneous disease has only begun to attract the attention of researchers. This review summarizes the data on the molecular mechanisms underlying DNA methylation and the MS risk factors that can affect the DNA methylation profile and, thereby, modulate the expression of the genes involved in the diseases pathogenesis. The focus of our attention is centered on the analysis of the published data on the differential methylation of DNA from various biological samples of MS patients obtained using both the candidate gene approach and high-throughput methods.

scholarly journals DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in the coral modelAiptasia

2017 ◽  
Author(s):  
Yong Li ◽  
Yi Jin Liew ◽  
Guoxin Cui ◽  
Maha J Cziesielski ◽  
Noura Zahran ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Model System ◽  
Epigenetic Mechanism ◽  
Symbiotic Relationship ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
Spurious Transcription ◽  
Coral Reef Ecosystems

The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research is focusing on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, which have been implicated in transcriptional regulation and acclimation to environmental change, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model systemAiptasia. We find methylated genes are marked by histone H3K36me3 and show significant reduction of spurious transcription and transcriptional noise, revealing a role of DNA methylation in the maintenance of transcriptional homeostasis. Changes in DNA methylation and expression show enrichment for symbiosis-related processes such as immunity, apoptosis, phagocytosis recognition and phagosome formation, and unveil intricate interactions between the underlying pathways. Our results demonstrate that DNA methylation provides an epigenetic mechanism of transcriptional homeostasis during symbiosis.

CpG methylation of an X-linked transgene is determined by somatic events postfertilization and not germline imprinting

Development ◽  
1988 ◽  
Vol 104 (2) ◽  
pp. 235-244
Author(s):  
A. Collick ◽  
W. Reik ◽  
S.C. Barton ◽  
A.H. Surani
Keyword(s):  
Dna Methylation ◽  
X Chromosome ◽  
De Novo ◽  
Cpg Methylation ◽  
Parental Origin ◽  
Cpg Dinucleotides ◽  
Inactive State ◽  
Methylation Of Dna ◽  
Methylation Patterns ◽  
Extraembryonic Tissues

The process of X-inactivation in mammals requires at least two events, the initiation of inactivation and the maintenance of the inactive state. One possible mechanism of control is by methylation of DNA at CpG dinucleotides to maintain the inactive state. Furthermore, the paternal X-chromosome is frequently inactivated in the extraembryonic membranes. The relationship between the parental origin of the chromosome, nonrandom inactivation and DNA methylation is not clear. In this paper, we report on the CpG methylation of an X-linked transgene, CAT-32. The levels of methylation in embryonic, extraembryonic and germline cells indicates that the modifications of the transgene are broadly similar to those reported for endogenous X-linked genes. Interestingly, the methylation of CAT-32 transgene in extraembryonic tissues displays patterns that could be linked to the germline origin of each allele. Hence, the maternally derived copy of CAT-32 was relatively undermethylated when compared to the paternal one. The changes in DNA methylation were attributed to de novo methylation occurring after fertilization, most probably during differentiation of extraembryonic tissues. In order to determine whether or not the patterns of DNA methylation reflected the germline origin of the X-chromosome, we constructed triploid embryos specifically to introduce two maternal X-chromosomes in the same embryo. In some of these triploid conceptuses, methylation patterns characteristic of the paternally derived transgene were observed. This observation indicates that the methylation patterns are not necessarily dependent on the parental origin of the X-chromosome, but could be changed by somatic events after fertilization. One of the more likely mechanisms is methylation of the transgene following inactivation of the X-chromosome in extraembryonic tissues.

scholarly journals Transcriptome and DNA Methylation Analyses of the Molecular Mechanisms Underlying with Longissimus dorsi Muscles at Different Stages of Development in the Polled Yak

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 970 ◽  
Author(s):  
Ma ◽  
Jia ◽  
Chu ◽  
Fu ◽  
Lei ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Methylation Status ◽  
Muscle Growth ◽  
Class Ii ◽  
Epigenetic Mechanism ◽  
Class I ◽  
Longissimus Dorsi ◽  
Growth Stages

DNA methylation modifications are implicated in many biological processes. As the most common epigenetic mechanism DNA methylation also affects muscle growth and development. The majority of previous studies have focused on different varieties of yak, but little is known about the epigenetic regulation mechanisms in different age groups of animals. The development of muscles in the different stages of yak growth remains unclear. In this study, we selected the longissimus dorsi muscle tissue at three different growth stages of the yak, namely, 90-day-old fetuses (group E), six months old (group M), and three years old (group A). Using RNA-Seq transcriptome sequencing and methyl-RAD whole-genome methylation sequencing technology, changes in gene expression levels and DNA methylation status throughout the genome were investigated during the stages of yak development. Each group was represented by three biological replicates. The intersections of expression patterns of 7694 differentially expressed genes (DEGs) were identified (padj < 0.01, |log2FC| > 1.2) at each of the three developmental periods. Time-series expression profile clustering analysis indicated that the DEGs were significantly arranged into eight clusters which could be divided into two classes (padj < 0.05), class I profiles that were downregulated and class II profiles that were upregulated. Based on this cluster analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEGs from class I profiles were significantly (padj < 0.05) enriched in 21 pathways, the most enriched pathway being the Axon guidance signaling pathway. DEGs from the class II profile were significantly enriched in 58 pathways, the pathway most strongly enriched being Metabolic pathway. After establishing the methylation profiles of the whole genomes, and using two groups of comparisons, the three combinations of groups (M-vs.-E, M-vs.-A, A-vs.-E) were found to have 1344, 822, and 420 genes, respectively, that were differentially methylated at CCGG sites and 2282, 3056, and 537 genes, respectively, at CCWGG sites. The two sets of data were integrated and the negative correlations between DEGs and differentially methylated promoters (DMPs) analyzed, which confirmed that TMEM8C, IGF2, CACNA1S and MUSTN1 were methylated in the promoter region and that expression of the modified genes was negatively correlated. Interestingly, these four genes, from what was mentioned above, perform vital roles in yak muscle growth and represent a reference for future genomic and epigenomic studies in muscle development, in addition to enabling marker-assisted selection of growth traits.

scholarly journals Introduction to Single-Cell DNA Methylation Profiling Methods

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1013
Author(s):  
Jongseong Ahn ◽  
Sunghoon Heo ◽  
Jihyun Lee ◽  
Duhee Bang
Keyword(s):  
Dna Methylation ◽  
Single Cell ◽  
Gene Expression Regulation ◽  
Epigenetic Mechanism ◽  
Computational Data ◽  
Dna Methylation Profiling ◽  
Differentiation Gene ◽  
Experimental Strategies ◽  
Methylation Profiling ◽  
Blind Spots

DNA methylation is an epigenetic mechanism that is related to mammalian cellular differentiation, gene expression regulation, and disease. In several studies, DNA methylation has been identified as an effective marker to identify differences between cells. In this review, we introduce single-cell DNA-methylation profiling methods, including experimental strategies and approaches to computational data analysis. Furthermore, the blind spots of the basic analysis and recent alternatives are briefly described. In addition, we introduce well-known applications and discuss future development.

scholarly journals Epigenetics and the Developmental Origins of Inflammatory Bowel Diseases

2012 ◽  
Vol 26 (12) ◽  
pp. 909-915 ◽  
Author(s):  
Richard Kellermayer
Keyword(s):  
Dna Methylation ◽  
Environmental Factors ◽  
Biological Networks ◽  
Molecular Mechanisms ◽  
Biological Systems ◽  
Environmental Influences ◽  
Monozygotic Twin ◽  
Host Immune System ◽  
Cpg Dinucleotides ◽  
Inflammatory Bowel

The gut microbiota, the intestinal mucosa and the host immune system are among the large biological networks involved in the development of inflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC). Host genetics and environmental factors can significantly modulate the interactive relationships among these biological systems and influence predilection toward IBD. High monozygotic twin discordance rates and the rapid rise in the prevalence of IBD indicate that environmental influences may be as important or even more important in their pathogenesis than genetic susceptibility. However, the nature and timing of environmental factors critical for inducing IBD remain largely unknown. The molecular mechanisms and the key biological component(s) that may be affected by such factors are also in question. Epigenetic changes, such as DNA methylation (the methylation of cytosines followed by a guanine in CpG dinucleotides) can be modified by environmental influences during finite developmental periods and have been implicated in the pathogenesis of IBD. Mucosal DNA methylation can also react to changes in the commensal microbiota, underscoring the intercalating relationships among the large biological systems involved in gastrointestinal disorders. Therefore, transient environmental influences during specific periods of development may induce critical change(s) in an isolated or concomitant fashion within the intestinal biomic networks and lead to increased susceptibility to IBD. The present review focuses on the emerging paradigm shift considering IBD to originate from critical environmental effects during pre- and postnatal development.

scholarly journals DNA Methylation in Neurodegenerative and Cerebrovascular Disorders

2020 ◽  
Vol 21 (6) ◽  
pp. 2220 ◽  
Author(s):  
Olaia Martínez-Iglesias ◽  
Iván Carrera ◽  
Juan Carlos Carril ◽  
Lucía Fernández-Novoa ◽  
Natalia Cacabelos ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Expression Regulation ◽  
Methylation Status ◽  
Cerebrovascular Disorders ◽  
Cerebrovascular Diseases ◽  
Epigenetic Mechanism ◽  
Mrna Levels ◽  
Serum Samples ◽  
Global Methylation ◽  
Age Related

DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is to compare methylation status of healthy subjects with that of patients with Alzheimer’s, Parkinson’s or Cerebrovascular diseases. We also analyze methylation status of a transgenic Alzheimer’s disease mouse model (3xTg-AD). Our results show that both global methylation (n = 141) and hydroxymethylation (n = 131) levels are reduced in DNA samples from buffy coats of patients with neurodegenerative disorders and age-related cerebrovascular disease. The importance of methylation and hydroxymethylation reduction is stressed by the finding that DNMT3a mRNA levels are also downregulated in buffy coats of patients with Dementia (n = 25). Global methylation is also reduced in brain, liver and serum samples of 3xTg-AD vs. wild type mice, such as DNMT3a mRNA levels that are also decreased in the brain of 3xTg-AD (n = 10). These results suggest that the use of global methylation and hydroxymethylation levels, together with the study of DNMT3a expression, could be useful as a new diagnostic biomarker for these prevalent disorders.

scholarly journals The Function of the Metals in Regulating Epigenetics During Parkinson’s Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiangzhen Wei ◽  
Menghua Cai ◽  
Lifang Jin
Keyword(s):  
Parkinson’S Disease ◽  
Dna Methylation ◽  
Central Nervous System ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Histone Modification ◽  
Motor System ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Global Hypomethylation

Parkinson’s means Parkinson’s disease, a chronic degenerative disease of central nervous system. The main area which is affected by this disease is motor system. Since it firstly founded by James Parkinson in his 1817 publication, nowadays, people still have lots of questions about this disease. This review mainly summarizes the epigenetics of Parkinson’s. DNA methylation is one of the epigenetic mechanisms of Parkinson’s. During the development of disease, global hypomethylation, and hypermethylation happen in different areas of patients. Another epigenetic mechanism is histone modification. People believe that some metals can induce Parkinson’s disease by modulating epigenetic mechanisms. This review summarizes the relationships between different metals and Parkinson’s disease. However, the specific roles of most metals in epigenetics are still unknown, which need further research.

scholarly journals Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

2016 ◽  
Vol 25 (140) ◽  
pp. 135-140 ◽  
Author(s):  
Prakash Chelladurai ◽  
Werner Seeger ◽  
Soni Savai Pullamsetti
Keyword(s):  
Dna Methylation ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Histone Deacetylases ◽  
Molecular Mechanisms ◽  
Epigenetic Mechanisms ◽  
Aberrant Expression ◽  
Genome Wide ◽  
A Genome ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a severe and progressive disease, characterised by high pulmonary artery pressure that usually culminates in right heart failure. Recent findings of alterations in the DNA methylation state of superoxide dismutase 2 and granulysin gene loci; histone H1 levels; aberrant expression levels of histone deacetylases and bromodomain-containing protein 4; and dysregulated microRNA networks together suggest the involvement of epigenetics in PAH pathogenesis. Thus, PAH pathogenesis evidently involves the interplay of a predisposed genetic background, epigenetic state and injurious events. Profiling the genome-wide alterations in the epigenetic mechanisms, such as DNA methylation or histone modification pattern in PAH vascular cells, may explain the great variability in susceptibility and disease severity that is frequently associated with pronounced remodelling and worse clinical outcome. Moreover, the influence of genetic predisposition and the acquisition of epigenetic alterations in response to environmental cues in PAH progression and establishment has largely been unexplored on a genome-wide scale. In order to gain insights into the molecular mechanisms leading to the development of PAH and to design novel therapeutic strategies, high-throughput approaches have to be adopted to facilitate systematic identification of the disease-specific networks using next-generation sequencing technologies, the application of these technologies in PAH has been relatively trivial to date.

scholarly journals A possible role of DNA methylation in functional divergence of a fast evolving duplicate gene encoding odorant binding protein 11 in the honeybee

2016 ◽  
Vol 283 (1833) ◽  
pp. 20160558 ◽  
Author(s):  
R. Kucharski ◽  
J. Maleszka ◽  
R. Maleszka
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Functional Divergence ◽  
Duplicate Gene ◽  
Epigenetic Mechanism ◽  
Duplicated Genes ◽  
Functional Diversification ◽  
Gene Encoding ◽  
Odorant Binding

Although gene duplication is seen as the main path to evolution of new functions, molecular mechanisms by which selection favours the gain versus loss of newly duplicated genes and minimizes the fixation of pseudo-genes are not well understood. Here, we investigate in detail a duplicate honeybee gene obp11 belonging to a fast evolving insect gene family encoding odorant binding proteins (OBPs). We report that obp11 is expressed only in female bees in rare antennal sensilla basiconica in contrast to its tandem partner obp10 that is expressed in the brain in both females and males (drones). Unlike all other obp genes in the honeybee, obp11 is methylated suggesting that functional diversification of obp11 and obp10 may have been driven by an epigenetic mechanism. We also show that increased methylation in drones near one donor splice site that correlates with higher abundance of a transcript variant encoding a truncated OBP11 protein is one way of controlling its contrasting expression. Our data suggest that like in mammals and plants, DNA methylation in insects may contribute to functional diversification of proteins produced from duplicated genes, in particular to their subfunctionalization by generating complementary patterns of expression.

scholarly journals Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes

2017 ◽  
Vol 24 (10) ◽  
pp. 1288-1300 ◽  
Author(s):  
Sabrina Ruhrmann ◽  
Ewoud Ewing ◽  
Eliane Piket ◽  
Lara Kular ◽  
Julio Cesar Cetrulo Lorenzi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dna Methylation ◽  
T Cells ◽  
Cd4 T Cells ◽  
Target Genes ◽  
Significant Negative Correlation ◽  
Chronic Inflammatory Disease ◽  
Epigenetic Mechanism ◽  
Relapsing Remitting ◽  
Genome Activity

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors. Objective: We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC). Methods: We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression. Results: We observed significant methylation differences in the VMP1/MIR21 locus, with RR-MS displaying higher methylation compared to SP-MS and HC. VMP1/MIR21 methylation did not correlate with a known MS risk variant in VMP1 or smoking but displayed a significant negative correlation with age and the levels of mature miR-21 in CD4+ T cells. Accordingly, RR-MS displayed lower levels of miR-21 compared to SP-MS, which might reflect differences in age between the groups, and healthy individuals and a significant enrichment of up-regulated miR-21 target genes. Conclusion: Disease-related changes in epigenetic marking of MIR21 in RR-MS lead to differences in miR-21 expression with a consequence on miR-21 target genes.

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