scholarly journals Protection of CpG islands from DNA methylation is DNA-encoded and evolutionarily conserved

2016 ◽  
Vol 44 (14) ◽  
pp. 6693-6706 ◽  
Author(s):  
Hannah K. Long ◽  
Hamish W. King ◽  
Roger K. Patient ◽  
Duncan T. Odom ◽  
Robert J. Klose
Keyword(s):  
Dna Methylation ◽  
Cpg Islands ◽  
Evolutionarily Conserved

Data Mining Technique Applied To DNA Sequencing

2015 ◽  
Vol 2 (7) ◽  
pp. 18
Author(s):  
R. Jamuna
Keyword(s):  
Data Mining ◽  
Dna Methylation ◽  
Markov Chain ◽  
Human Genome ◽  
Transition Probabilities ◽  
Markov Chain Model ◽  
Effective Means ◽  
Cpg Islands ◽  
Chain Model ◽  
The Given

CpG islands (CGIs) play a vital role in genome analysis as genomic markers.  Identification of the CpG pair has contributed not only to the prediction of promoters but also to the understanding of the epigenetic causes of cancer. In the human genome [1] wherever the dinucleotides CG occurs the C nucleotide (cytosine) undergoes chemical modifications. There is a relatively high probability of this modification that mutates C into a T. For biologically important reasons the mutation modification process is suppressed in short stretches of the genome, such as ‘start’ regions. In these regions [2] predominant CpG dinucleotides are found than elsewhere. Such regions are called CpG islands. DNA methylation is an effective means by which gene expression is silenced. In normal cells, DNA methylation functions to prevent the expression of imprinted and inactive X chromosome genes. In cancerous cells, DNA methylation inactivates tumor-suppressor genes, as well as DNA repair genes, can disrupt cell-cycle regulation. The most current methods for identifying CGIs suffered from various limitations and involved a lot of human interventions. This paper gives an easy searching technique with data mining of Markov Chain in genes. Markov chain model has been applied to study the probability of occurrence of C-G pair in the given   gene sequence. Maximum Likelihood estimators for the transition probabilities for each model and analgously for the  model has been developed and log odds ratio that is calculated estimates the presence or absence of CpG is lands in the given gene which brings in many  facts for the cancer detection in human genome.

scholarly journals Two competing mechanisms of DNMT3A recruitment regulate the dynamics of de novo DNA methylation at PRC1-targeted CpG islands

2021 ◽  
Author(s):  
Daniel N. Weinberg ◽  
Phillip Rosenbaum ◽  
Xiao Chen ◽  
Douglas Barrows ◽  
Cynthia Horth ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Cpg Islands

scholarly journals DNA Methylation of Human Choline Kinase Alpha Promoter-Associated CpG Islands in MCF-7 Cells

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 853
Author(s):  
Siti Aisyah Faten Mohamed Sa’dom ◽  
Sweta Raikundalia ◽  
Shaharum Shamsuddin ◽  
Wei Cun See Too ◽  
Ling Ling Few
Keyword(s):  
Dna Methylation ◽  
Transcription Factor ◽  
Binding Site ◽  
Promoter Activity ◽  
Cytosine Methylation ◽  
Cpg Island ◽  
Cpg Islands ◽  
Site Directed Mutagenesis ◽  
Choline Kinase ◽  
Mcf 7

Choline kinase (CK) is the enzyme catalyzing the first reaction in CDP-choline pathway for the biosynthesis of phosphatidylcholine. Higher expression of the α isozyme of CK has been implicated in carcinogenesis, and inhibition or downregulation of CKα (CHKA) is a promising anticancer approach. This study aimed to investigate the regulation of CKα expression by DNA methylation of the CpG islands found on the promoter of this gene in MCF-7 cells. Four CpG islands have been predicted in the 2000 bp promoter region of ckα (chka) gene. Six CpG island deletion mutants were constructed using PCR site-directed mutagenesis method and cloned into pGL4.10 vectors for promoter activity assays. Deletion of CpG4C region located between –225 and –56 significantly increased the promoter activity by 4-fold, indicating the presence of important repressive transcription factor binding site. The promoter activity of methylated full-length promoter was significantly lower than the methylated CpG4C deletion mutant by 16-fold. The results show that DNA methylation of CpG4C promotes the binding of the transcription factor that suppresses the promoter activity. Electrophoretic mobility shift assay analysis showed that cytosine methylation at MZF1 binding site in CpG4C increased the binding of putative MZF1 in nuclear extract. In conclusion, the results suggest that DNA methylation decreased the promoter activity by promoting the binding of putative MZF1 transcription factor at CpG4C region of the ckα gene promoter.

scholarly journals PGC7 suppresses TET3 for protecting DNA methylation

2013 ◽  
Vol 42 (5) ◽  
pp. 2893-2905 ◽  
Author(s):  
Chunjing Bian ◽  
Xiaochun Yu
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanism ◽  
Biological Process ◽  
Cpg Islands ◽  
Binding Motifs ◽  
Genome Wide Analysis ◽  
Dna Motif ◽  
Genome Wide

Abstract Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5-hydroxylmethylcytosine. However, the molecular mechanism that regulates this biological process is not clear. Here, we show the evidence that PGC7 (also known as Dppa3 or Stella) interacts with TET2 and TET3 both in vitro and in vivo to suppress the enzymatic activity of TET2 and TET3. Moreover, lacking PGC7 induces the loss of DNA methylation at imprinting loci. Genome-wide analysis of PGC7 reveals a consensus DNA motif that is recognized by PGC7. The CpG islands surrounding the PGC7-binding motifs are hypermethylated. Taken together, our study demonstrates a molecular mechanism by which PGC7 protects DNA methylation from TET family enzyme-dependent oxidation.

scholarly journals Pilot study of DNA methylation in the pathogenesis of chronic rhinosinusitis with nasal polyps

2015 ◽  
Vol 53 (4) ◽  
pp. 345-352
Author(s):  
Y.B. Zheng ◽  
Y. Zhao ◽  
L.Y. Yue ◽  
P. Lin ◽  
Y.F. Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Polymerase Chain Reaction ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Cpg Islands ◽  
Inferior Turbinate ◽  
Control Group ◽  
Chain Reaction ◽  
Bisulphite Sequencing ◽  
Polymerase Chain

Background: DNA methylation has been implicated in the pathogenesis of allergy and atopy. This study aimed to identify whether DNA methylation also plays an important role in the pathogenesis of nasal polyps (NP). Methodology: NP tissues were obtained from 32 patients with chronic rhinosinusitis with bilateral NP. Biopsies of inferior turbinate mucosa (ITM) were taken from 18 patients who underwent rhinoseptoplasty (control group). The methylated genes, which were detected by DNA methylation microarray, were validated by methylation-specific polymerase chain reaction, bisulphite sequencing, real-time polymerase chain reaction and immunohistochemistry. Results: DNA methylation microarray identified 8,008 CpG islands in 2,848 genes. One hundred and ninety-eight genes were found to have a methylated signal in the promoter region in NP samples compared with ITM samples. The four top genes that changed, COL18A1, EP300, GNAS and SMURF1, were selected for further study. The methylation frequency of COL18A1 was significantly higher in NP samples than in ITM samples. Conclusions: DNA methylation might play an important role in the pathogenesis of NP. Promoter methylation of COL18A1 was found to be significantly increased in NP tissues, further studies are necessary to confirm the significance of these epigenetic factors in the mechanisms underlying the development or persistence of NP.

scholarly journals Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status

2021 ◽  
Author(s):  
Ilhame Diboun ◽  
Sachin Wani ◽  
Stuart H Ralston ◽  
Omar M E Albagha
Keyword(s):  
Dna Methylation ◽  
Meta Analysis ◽  
Cpg Islands ◽  
Osteoclast Differentiation ◽  
Paget’S Disease ◽  
Disease Status ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Paget's Disease Of Bone ◽  
Body Regions

AbstractPaget’s Disease of Bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB associated changes in DNA methylation profiles in patients’ blood. Meta-analysis of data from the discovery and replication set, comprising of 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through eQTM analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the replication with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.

Abstract 428: DNA Methylation of ASC is Associated with Decreased ASC and IL-1β Expression in Heart Failure

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Brittany Butts ◽  
Javed Butler
Keyword(s):  
Heart Failure ◽  
Dna Methylation ◽  
Inflammatory Cytokines ◽  
Epigenetic Modification ◽  
Cpg Islands ◽  
Inflammasome Activation ◽  
Cpg Sites ◽  
Exon 1 ◽  
Vital Component ◽  
Intron Region

Introduction: Heart failure (HF) is associated with formation and activation of inflammasome, a complex of intracellular interaction proteins that trigger maturation of inflammatory cytokines to initiate inflammatory response. ASC, a vital component of the inflammasome, is controlled through epigenetic modification via methylation of CpG islands surrounding exon 1. Methods: To assess the relationships between DNA methylation of ASC, ASC expression, and inflammatory cytokines IL-1β and IL-18 in HF, stored samples from 155 chronic HF patients (age 56.9±12.0 yr, 64% male, 47% black, and ejection fraction 29.9±14.9) were analyzed. DNA extracted from PMBCs were analyzed by pyrosequencing for percent methylation of seven CpG sites in the intron region preceding exon 1 of the ASC gene. ASC mRNA was quantified via real-time PCR and analyzed as the ratio ASC:GAPDH. Serum ASC, IL-1β, and IL-18 were measured by ELISA. Results: Higher ASC methylation was associated with lower ASC mRNA (r=0-.328, p<0.001) and protein (r=-.464, p<0.001) expression. Lower ASC mRNA expression was associated with lower ASC protein expression (r=0.494, p<0.001). Decreased IL-1β expression was associated with higher ASC methylation (r=-.424, p=0.005) and lower ASC mRNA (r=.619, p<0.001) and ASC protein (r=.433, p<0.001). IL-18 expression was not significantly associated with ASC methylation or expression. Conclusions: Increased ASC methylation was associated with lower IL-1β, likely via decreased ASC gene expression. As ASC is required for inflammasome activation of IL-1β, this study implicates the inflammasome pathway as a driver of inflammation in HF, proving a potential target for novel interventions.

Rare sequence variation and DNA methylation : effects on alcohol and tobacco use phenotypes

2019 ◽  
Author(s):  
◽  
Jacqueline Marisa Otto
Keyword(s):  
Dna Methylation ◽  
Tobacco Use ◽  
Sequence Variation ◽  
Rare Variants ◽  
Cpg Islands ◽  
Protein Coding ◽  
University Of Missouri ◽  
Rare Variation ◽  
The University ◽  
Regulatory Dna

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Alcohol and tobacco use and dependence are known to be influenced by the effects of common variants enriched in non-coding gene regulatory regions, as well as rare protein-coding variation. In contrast, the role of rare non-coding regulatory variation is unknown. Epigenetic factors such as DNA methylation also influence gene expression, and some of these effects are under genomic control. The current study investigated the effects of rare coding and non-coding variation in regions susceptible to DNA methylation, and whether differential levels of methylation mediated their effects in association with alcohol and tobacco use and dependence. Data from whole-genome sequencing and DNA methylation microarrays for participants in the UCSF Family Alcoholism Study (N = 1,852) were used for set-based tests of rare variation, region-based differential methylation, and epigenetic mediation in relation to quantitative measures of alcohol and tobacco use and DSM-IV dependence diagnoses. Rare variants in exonic and intronic regions, as well as CpG islands, were weighted by a measure of deleteriousness and were significantly associated with alcohol and tobacco use phenotypes. Similarly, differential levels of DNA methylation exhibited significant association with lifetime and current measures of use and dependence. However, there was a relative lack of evidence for epigenetic mediation of rare variation, likely due to a lack of power. Findings from the current study suggest that rare regulatory DNA sequence variation and differential levels of DNA methylation influence risk for alcohol and tobacco use, but whether there exists epigenetic mediation of rare variation requires larger sample sizes in future studies.

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