scholarly journals The DNA methylation level against the background of the genome size and t-heterochromatin content in some species of the genusSecale L

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2889 ◽  
Author(s):  
Anna Kalinka ◽  
Magdalena Achrem ◽  
Paulina Poter

Methylation of cytosine in DNA is one of the most important epigenetic modifications in eukaryotes and plays a crucial role in the regulation of gene activity and the maintenance of genomic integrity. DNA methylation and other epigenetic mechanisms affect the development, differentiation or the response of plants to biotic and abiotic stress. This study compared the level of methylation of cytosines on a global (ELISA) and genomic scale (MSAP) between the species of the genusSecale. We analyzed whether the interspecific variation of cytosine methylation was associated with the size of the genome (C-value) and the content of telomeric heterochromatin. MSAP analysis showed thatS. sylvestrewas the most distinct species among the studied rye taxa; however, the results clearly indicated that these differences were not statistically significant. The total methylation level of the studied loci was very similar in all taxa and ranged from 60% inS. strictumssp.africanumto 66% inS. cerealessp.segetale, which confirmed the lack of significant differences in the sequence methylation pattern between the pairs of rye taxa. The level of global cytosine methylation in the DNA was not significantly associated with the content of t-heterochromatin and did not overlap with the existing taxonomic rye relationships. The highest content of 5-methylcytosine was found inS. cerealessp.segetale(83%), while very low inS. strictumssp.strictum(53%), which was significantly different from the methylation state of all taxa, except forS. sylvestre. The other studied taxa of rye had a similar level of methylated cytosine ranging from 66.42% (S. vavilovii) to 74.41% in (S. cerealessp.afghanicum). The results obtained in this study are evidence that the percentage of methylated cytosine cannot be inferred solely based on the genome size or t-heterochromatin. This is a significantly more complex issue.

2018 ◽  
Vol 13 (1) ◽  
pp. 327-334 ◽  
Author(s):  
Xiaowu Chen ◽  
Yonghua Zhao ◽  
Yudong He ◽  
Jinliang Zhao

AbstractSkewed sex development is prevalent in fish hybrids. However, the histological observation and molecular mechanisms remain elusive. In this study, we showed that the interspecific hybrids of the two fish species, Oreochromis niloticus and Oreochromis aureus, had a male ratio of 98.02%. Microscopic examination revealed that the gonads of both male and female hybrids were developmentally retarded. Compared with the ovaries, the testes of both O. niloticus and hybrids showed higher DNA methylation level in two selected regions in the promoter of cyp19a, the gonadal aromatase gene that converts androgens into estrogens, cyp19a showed higher level gene expression in the ovary than in the testis in both O. niloticus and hybrid tilapia. Methylation and gene expression level of cyp19a were negative correlation between the testis and ovary. Gene transcription was suppressed by the methylation of the cyp19a promoter in vitro. While there is no obvious difference of the methylation level in testis or ovary between O. niloticus and hybrids. Thus, the DNA methylation of the promoter of cyp19a may be an essential component of the sex maintenance, but not a determinant of high male ratio and developmental retardation of gonads in tilapia hybrids.


2013 ◽  
Vol 25 (2) ◽  
pp. 66-76 ◽  
Author(s):  
Yaping Hou ◽  
Huayun Chen ◽  
Qiong He ◽  
Wei Jiang ◽  
Tao Luo ◽  
...  

BackgroundEfforts aiming at identifying biomarkers and corresponding methods for early diagnosis of Alzheimer's disease (AD) might be the most appropriate strategy to initiate promising new treatments and/or prevention of ADObjectiveThe aim of our study is to assess the association of DNA methylation pattern of various leucocyte genes with AD pathogenesis in order to find potential biomarkers and corresponding methods for molecular diagnosis of AD.MethodsDNA methylation level of various genes in AD patients and normal population were compared by bisulphite sequencing PCR and methylation-specific PCR (MSP). Furthermore, real-time PCR was used to explore the effects of DNA methylation on the expression of target genes.ResultsResults showed significant hypermethylation of mammalian orthologue of Sir2 (SIRT1) gene in AD patients compared with normal population. Meanwhile, changes in methylation level of SIRT1 gene between different severities of AD were also found. Specific primers were designed from the SIRT1 CpG islands to differentiate AD and control group by MSP method. Besides, significant demethylation of β-amyloid precursor protein (APP) gene was observed in AD patients, whereas no difference was observed in other AD-related genes. Moreover, significant decrease in expression of SIRT1 gene and increase in expression of APP gene were also found in AD patients. In addition, the expression level of SIRT1/APP genes was associated with the severity, but not with the age or gender, of AD patients.Conclusion:SIRT1 and APP might be the interesting candidate biomarkers and valuable for clinical diagnosis or treatment of AD.


Author(s):  
Lei Zhao ◽  
Xiaosheng Chen ◽  
Shengjun Zhou ◽  
Zhiqing Lin ◽  
Xi Yu ◽  
...  

Genetic factors play an important role in the pathogenesis of ischemic stroke. Of these, epigenetic modifications provide a new direction for the study of ischemic stroke pathogenesis. This study aimed to determine the correlation between DNA methylation of the gene encoding S-adenosylhomocysteine hydrolase (AHCY) and the risk of ischemic stroke in 64 ischemic stroke patients and 138 patients with traumatic brain injury (control group). The methylation level of AHCY was analyzed using quantitative methylation-specific polymerase chain reaction. Statistically significant differences in AHCY methylation levels were observed between the case group [medians (interquartile range): 0.13% (0.09%, 0.27%)] and the control group [0.06% (0.00%, 0.17%), p < 0.0001], and these associations remained significant in both male (p = 0.003) and female (p = 0.0005) subjects. A subgroup analysis by age revealed a considerably higher percentage of methylated AHCY in the case group than the control group in all age groups (age < 60 years, p = 0.007; age ≥ 60 years, p < 0.0001). A receiver operating characteristic (ROC) curve analysis revealed a trend toward a role for AHCY methylation as an indicator of risk in all ischemic patients [area under the curve (AUC) = 0.70, p = 0.0001], male patients (AUC = 0.67, p = 0.004), and female patients (AUC = 0.75, p = 0.0002). Our study confirmed a significant association between the AHCY DNA methylation level and the risk of ischemic stroke, suggesting that this gene methylation pattern may be a potential diagnostic marker of ischemic stroke.


Author(s):  
Jinpu Cai ◽  
Yuyang Xu ◽  
Wen Zhang ◽  
Shiying Ding ◽  
Yuewei Sun ◽  
...  

Abstract Motivation: DNA methylation is a biological process impacting the gene functions without changing the underlying DNA sequence. The DNA methylation machinery usually attaches methyl groups to some specific cytosine residues, which modify the chromatin architectures. Such modifications in the promoter regions will inactivate some tumor-suppressor genes. DNA methylation within the coding region may significantly reduce the transcription elongation efficiency. The gene function may be tuned through some cytosines are methylated. Methods: This study hypothesizes that the overall methylation level across a gene may have a better association with the sample labels like diseases than the methylations of individual cytosines. The gene methylation level is formulated as a regression model using the methylation levels of all the cytosines within this gene. A comprehensive evaluation of various feature selection algorithms and classification algorithms is carried out between the gene-level and residue-level methylation levels. Results: A comprehensive evaluation was conducted to compare the gene and cytosine methylation levels for their associations with the sample labels and classification performances. The unsupervised clustering was also improved using the gene methylation levels. Some genes demonstrated statistically significant associations with the class label, even when no residue-level methylation features have statistically significant associations with the class label. So in summary, the trained gene methylation levels improved various methylome-based machine learning models. Both methodology development of regression algorithms and experimental validation of the gene-level methylation biomarkers are worth of further investigations in the future studies. The source code, example data files and manual are available at http://www.healthinformaticslab.org/supp/.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 225.1-225
Author(s):  
E. Punceviciene ◽  
J. Gaizevska ◽  
R. Sabaliauskaite ◽  
L. Venceviciene ◽  
D. Vitkus ◽  
...  

Background:Vitamin D is known for its immunomodulatory and epigenome interacting effects. Vitamin D deficiency is frequently observed in rheumatoid arthritis (RA) patients compared to healthy controls, is also named as a potential risk factor in RA ethiopatogenesis and may alter DNA methylation of certain genes [1,2]. Still, causality of vitamin D deficiency in RA patients needs to be elucidated.Objectives:The aim of the study was to evaluate relationship between DNA methylation status of vitamin D related genes (VDR,CYP24A1,CYP2R1), miRNA-155 expression, vitamin D level and its association with RA.Methods:CpG islands in promoter region of theVDR,CYP24A1,CYP2R1genes were chosen for DNA methylation analysis by means of pyrosequencing. DNA from blood mononuclear cells of 31 RA patients and 31 age and sex matched healthy controls was assessed for methylation pattern after informed consent was obtained in Vilnius university Hospital Santaros klinikos Centre of Rheumatology. For miRNA analysis quantitative reverse transcription PCR was used. Chemiluminescent microplate immunoassay was used to asses 25(OH)D serum levels.Results:25(OH)D concentrations varied from deficiency (<50 nmol/l), insufficiency (50-75 nmol/l) to normal range (≥75-100 nmol/l) in RA (mean 47.49 nmol/l; SD ± 27.93) and healthy controls (mean 57.38 nmol/l; SD ± 29.93)).CYP24A1methylation level was significantly higher in comparison toVDR(p<0.0001) andCYP2R1(p<0.0001) genes in both groups.CYP24A1hypermethylation was also observed in older subjects (p=0.012). The study demonstrated a significant positive correlation between vitamin D concentration andVDR,CYP2R1genes methylation intensity (r2=0.31, p=0.014; r2=0.25, p=0.042, respectively). However, gene methylation frequency and methylation intensity showed no significant difference between RA patients and healthy controls (VDR– 2.4vs2.6 %,CYP24A1– 16.6vs15.3 %,CYP2R1– 2.6vs2.6 %) (p>0.05). To note, miRNA-155 expression negatively correlated withCYP24A1methylation intensity (r2=-0.43, p=0.009).Conclusion:Our study identified significant associations between theVDRandCYP2R1promoter methylation and vitamin D concentration. However, no significant differences in DNA methylation pattern between RA patients and healthy controls were detected. MiR-155 expression was associated withCYP24A1methylation level, confirming its possible involvement in vitamin D metabolism. The data of our study suggests that epigenetic phenomena are significantly involved in vitamin D metabolism and may have an indirect effect on RA ethiopatogenesis.References:[1]Jeffery LE, et al. Nat Rev Rheumatol. 2016,12.4:201.[2]Fetahu IS et al. Front Physiol. 2014,5:164.Acknowledgments:This project has received funding from the Research Council of Lithuania (LMTLT), agreement No. S-MIP-17-12.Disclosure of Interests:None declared


2020 ◽  
Vol 21 (16) ◽  
pp. 5753
Author(s):  
Linying Li ◽  
Yuqing He ◽  
Xueying Zhang ◽  
Hehong Zhang ◽  
Zongtao Sun ◽  
...  

Rice black-streaked dwarf virus (RBSDV) causes severe yield losses in rice (Oryza sativa L.) in China. Studies have shown that the mechanisms of DNA methylation-mediated plant defense against DNA viruses and RNA viruses are different. However, in rice its function in response to infection of RBSDV, a double-stranded RNA virus, remains unclear. In this study, high-throughput single-base resolution bisulfite sequencing (BS-Seq) was carried out to analyze the distribution pattern and characteristics of cytosine methylation in RBSDV-infected rice. Widespread differences were identified in CG and non-CG contexts between the RBSDV-infected and RBSDV-free rice. We identified a large number of differentially methylated regions (DMRs) along the genome of RBSDV-infected rice. Additionally, the transcriptome sequencing analysis obtained 1119 differentially expressed genes (DEGs). Correlation analysis of DMRs-related genes (DMGs) and DEGs filtered 102 genes with positive correlation and 71 genes with negative correlation between methylation level at promoter regions and gene expression. Key genes associated with maintaining DNA methylation in rice were analyzed by RT-qPCR and indicated that OsDMT702 might be responsible for the global increase of DNA methylation level in rice under RBSDV stress. Our results suggest important roles of rice DNA methylation in response to RBSDV and provide potential target genes for rice antiviral immunity.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Yu Zhang ◽  
Meiyu Tan ◽  
Xiaoqiong Qian ◽  
Cong Li ◽  
Lei Yue ◽  
...  

Abstract Background Recent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes. We investigated whether AR susceptibility genes were epigenetically regulated, and whether methylation modulation of these genes in response to early-life environment could be a molecular mechanism underlying the risk for AR onset in a cohort of children aged 3–6 years in China. Methods Peripheral blood mononuclear cell (PBMC) samples were collected from 130 children patients, aged 3–6 years and diagnosed with AR; and 154 matched controls to detect promoter methylation in 25 AR susceptibility genes with the MethylTarget approach. Methylation levels were compared for each CpG site, each amplified region, and each gene. In addition, the relationship among DNA methylation, early-life environmental risk factors and AR onset were assessed. Results Maternal allergic history (P = 0.0390) and pet exposure (P = 0.0339) were significantly associated with increased AR risk. Differential methylation analyses were successfully performed for 507 CpG sites, 34 amplified regions and 17 genes and significant hypomethylation was observed in the promoter region of ADAM33 in AR patients [multiple test-corrected (FDR) P-value < 0.05]. Spearman correlation analysis revealed that the hypomethylation of ADAM33 was significantly associated with higher eosinophil counts (Spearman’s ρ: − 0.187, P-value = 0.037). According to the results of the multiple regression analysis, after adjusting for cofounders, the interaction of early-life pet exposure with methylation level of ADAM33 increased the risk for AR onset 1.423 times more in children (95% CI = 0.0290–4.109, P-value = 0.005). Conclusion This study provides evidence that early-life pet exposure and low methylation level of ADAM33 increase AR risk in children, and the interaction between pet exposure and methylation level of ADAM33 may play an important role in the development of AR.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Michele Zampieri ◽  
Maria Giulia Bacalini ◽  
Ilaria Barchetta ◽  
Stefania Scalea ◽  
Flavia Agata Cimini ◽  
...  

Abstract Background Epigenetic modifications, such as DNA methylation, can influence the genetic susceptibility to type 2 diabetes mellitus (T2DM) and the progression of the disease. Our previous studies demonstrated that the regulation of the DNA methylation pattern involves the poly(ADP-ribosyl)ation (PARylation) process, a post-translational modification of proteins catalysed by the poly(ADP-ribose) polymerase (PARP) enzymes. Experimental data showed that the hyperactivation of PARylation is associated with impaired glucose metabolism and the development of T2DM. Aims of this case–control study were to investigate the association between PARylation and global and site-specific DNA methylation in T2DM and to evaluate metabolic correlates. Results Data were collected from 61 subjects affected by T2DM and 48 healthy individuals, recruited as controls. Global levels of poly(ADP-ribose) (PAR, a surrogate of PARP activity), cytosine methylation (5-methylcytosine, 5mC) and de-methylation intermediates 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) were determined in peripheral blood cells by ELISA-based methodologies. Site-specific DNA methylation profiling of SOCS3, SREBF1 and TXNIP candidate genes was performed by mass spectrometry-based bisulfite sequencing, methyl-sensitive endonucleases digestion and by DNA immuno-precipitation. T2DM subjects presented higher PAR levels than controls. In T2DM individuals, increased PAR levels were significantly associated with higher HbA1c levels and the accumulation of the de-methylation intermediates 5hmC and 5fC in the genome. In addition, T2DM patients with higher PAR levels showed reduced methylation with increased 5hmC and 5fC levels in specific SOCS3 sites, up-regulated SOCS3 expression compared to both T2DM subjects with low PAR levels and controls. Conclusions This study demonstrates the activation of PARylation processes in patients with T2DM, particularly in those with poor glycaemic control. PARylation is linked to dysregulation of DNA methylation pattern via activation of the DNA de-methylation cascade and may be at the basis of the differential gene expression observed in presence of diabetes.


Author(s):  
Aisha Alrofaidi ◽  
Rawan Saeed Alghamdi ◽  
Mona Alharbi ◽  
Khloud Algothmi ◽  
Reem Farsi ◽  
...  

The potential role of DNA methylation pattern in autism has been provided by revealing the differences in methylation level of multiple genes which are significantly associated with their expression and implicated in ASD pathogenesis. RASA3 is a member of GTPase-activating proteins, RASA3 is highly expressed in brain tissues and can be deregulated by different epigenetic mechanisms. Many studies reported that differentially expressed RASA3 is correlated with its aberrant methylation. Accordingly, this has been suggested that deferentially expression of RASA3 may be correlated with its methylation levels which could play a role in ASD which brought our attention to identify differentially-expressed genes that could be associated with their methylation level of ASD in Saudi population, by performing comparative gene expression of RASA3 then investigate its relation to methylation level. This study was conducted on 18 Saudi autistic children as well as their healthy-control siblings. Relative expression of a candidate gene (RASA3) was measured using RT-qPCR. Furthermore, MethyLight assay was performed to estimate methylation level and evaluate its impact on RASA3 expression. Interestingly, RASA3 expression has found to be dysregulated in ASD cases. In contrast, MethyLight assay result showed no differences in the methylation patterns among ASD cases in the candidate region. However, it remains an open question whether these dysregulations of RASA3 expression could be a biomarker for early screening/detection of some cases which may also suggest a role for RasGAPs in autistic brain function.


Sign in / Sign up

Export Citation Format

Share Document