Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.

Advances in microfluidic-based DNA methylation analysis

DNA methylation has been extensively investigated in recent years,not least because of its known relationship with various diseases.Progress in analytical methods can greatly increase the relevance of DNA methylation studies to both clinical medicine and scientific research.Microflu-idic chips are excellent carriers for molecular analysis,and their use can provide improvements from multiple aspects.On-chip molecular analysis has received extensive attention owing to its advantages of portability,high throughput,low cost,and high efficiency.In recent years,the use of novel microfluidic chips for DNA methylation analysis has been widely reported and has shown obvious superiority to conventional methods.In this review,wefirst focus on DNA methylation and its applications.Then,we discuss advanced microfluidic-based methods for DNA methylation analysis and describe the great progress that has been made in recent years.Finally,we summarize the advantages that microfluidic technology brings to DNA methylation analysis and describe several challenges and perspectives for on-chip DNA methylation analysis.This review should help researchers improve their understanding and make progress in developing microfluidic-based methods for DNA methylation analysis.

Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

DNA methylation in poultry:a review

As an important epigenetic modification,DNA methylation is involved in many biological processes such as animal cell differentiation,embryonic development,genomic imprinting and sex chromosome inactivation.As DNA methylation sequencing becomes more sophisticated,it becomes possible to use it to solve more zoological problems.This paper reviews the characteristics of DNA methylation,with emphasis on the research and application of DNA methylation in poultry.

Rice melatonin deficiency causes premature leaf senescence via DNA methylation regulation

In a study of DNA methylation changes in melatonin-deficient rice mutants,mutant plants showed premature leaf senescence during grain-filling and reduced grain yield.Melatonin deficiency led to transcriptional reprogramming,especially of genes involved in chlorophyll and carbon metabolism,redox regulation,and transcriptional regulation,during dark-induced leaf senescence.Hypomethylation of mCG and mCHG in the melatonin-deficient rice mutants was associated with the expression change of both protein-coding genes and transposable element-related genes.Changes in gene expression and DNA methylation in the melatonin-deficient mutants were compensated by exogenous application of melatonin.A decreased S-adenosyl-L-methionine level may have contributed to the DNA methylation variations in rice mutants of melatonin deficiency under dark conditions.

Advances in DNA methylation and its role in cytoplasmic male sterility in higher plants

The impact of epigenetic modifications like DNA methylation on plant phenotypes has expanded the possibilities for crop development.DNA methylation plays a part in the regulation of both the chromatin structure and gene expression,and the enzyme involved,DNA methyltransferase,executes the methylation process within the plant genome.By regulating crucial biological pathways,epigenetic changes actively contribute to the creation of the phenotype.Therefore,epigenome editing may assist in overcoming some of the drawbacks of genome editing,which can have minor off-target consequences and merely facilitate the loss of a gene’s function.These drawbacks include gene knockout,which can have such off-target effects.This review provides examples of several molecular characteristics of DNA methylation,as well as some plant physiological processes that are impacted by these epigenetic changes in the plants.We also discuss how DNA alterations might be used to improve crops and meet the demands of sustainable and environmentally-friendly farming.

Comparative DNA methylation reveals epigenetic adaptation to high altitude in snub-nosed monkeys

DNA methylation plays a crucial role in environmental adaptations.Here,using whole-genome bisulfite sequencing,we generated comprehensive genome-wide DNA methylation profiles for the high-altitude Yunnan snub-nosed monkey(Rhinopithecus bieti)and the closely related golden snub-nosed monkey(R.roxellana).Our findings indicated a slight increase in overall DNA methylation levels in golden snub-nosed monkeys compared to Yunnan snub-nosed monkeys,suggesting a higher prevalence of hypermethylated genomic regions in the former.Comparative genomic methylation analysis demonstrated that genes associated with differentially methylated regions were involved in membrane fusion,vesicular formation and trafficking,hemoglobin function,cell cycle regulation,and neuronal differentiation.These results suggest that the high-altitude-related epigenetic modifications are extensive,involving a complete adaptation process from the inhibition of single Ca^(2+)channel proteins to multiple proteins collaboratively enhancing vesicular function or inhibiting cell differentiation and proliferation.Functional assays demonstrated that overexpression or down-regulation of candidate genes,such as SNX10,TIMELESS,and CACYBP,influenced cell viability under stress conditions.Overall,this research suggests that comparing DNA methylation across closely related species can identify novel candidate genomic regions and genes associated with local adaptations,thereby deepening our understanding of the mechanisms underlying environmental adaptations.

DNA Methylation of KLRC1 and KLRC3 in Autoimmune Thyroiditis:Perspective of Different Water Iodine Exposure

Objective This study aimed to identify differentially methylated genes(DMGs) associated with natural killer cells in patients with autoimmune thyroiditis(AIT), focusing on the influence of varying water iodine exposure levels.Methods Participants were divided into categories based on median water iodine(MWI)concentrations: iodine-fortified areas(IFA, MWI < 10 μg/L), iodine-adequate areas(IAA, 40 ≤ MWI ≤ 100μg/L), and iodine-excessive areas(IEA, MWI > 300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89, 40, and 47 pairs for IFA, IAA, and IEA, respectively. DMGs were identified using 850K Bead Chip analysis for 10/10 paired samples. Validation of DNA methylation and m RNA expression levels of the DMGs was conducted using Methyl Target^(TM) and QRT-PCR for 176/176paired samples.Results KLRC1, KLRC3, and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed, whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore, KLRC1 was hypomethylated and highly expressed in both IFA and IEA.Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally, DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population

BACKGROUND Colorectal cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.Syndecan-2 methylation(mSDC2)testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.Cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.AIM To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China.METHODS A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing.Sensitivity and specificity for CRC,advanced adenoma(AA)and advanced colorectal neoplasia(ACN)were determined.High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test.RESULTS A total of 1035 high-risk individuals were included in this study according to established criteria.Among them,16 suffered from CRC(1.55%),65 from AA(6.28%)and 189 from non-AAs(18.26%);150 patients were diagnosed with polyps(14.49%).Diagnoses were established based upon colonoscopic and pathological examinations.Sensitivities of the mSDC2 test for CRC and AA were 87.50%and 40.00%,respectively;specificities were 95.61%for other groups.Positive predictive values of the mSDC2 test for CRC,AA and ACN were 16.09%,29.89%and 45.98%,respectively;the negative predictive value for CRC was 99.79%.After adjusting for other high-risk covariates,mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN(P<0.001).CONCLUSION Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Methylome and transcriptome data integration reveals potential roles of DNA methylation and candidate biomarkers of cow Streptococcus uberis subclinical mastitis

Background:Mastitis caused by different pathogens including Streptococcus uberis(S.uberis)is responsible for huge economic losses to the dairy industry.In order to investigate the potential genetic and epigenetic regulatory mecha‑nisms of subclinical mastitis due to S.uberis,the DNA methylome(whole genome DNA methylation sequencing)and transcriptome(RNA sequencing)of milk somatic cells from cows with naturally occurring S.uberis subclinical mastitis and healthy control cows(n=3/group)were studied.Results:Globally,the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and introns.The DNA methylation levels at the promoter,first exon and first intron regions were nega‑tively correlated with the expression level of genes at a whole‑genome‑wide scale.In general,DNA methylation level was lower in S.uberis‑positive group(SUG)than in the control group(CTG).A total of 174,342 differentially methylated cytosines(DMCs)(FDR<0.05)were identified between SUG and CTG,including 132,237,7412 and 34,693 DMCs in the context of CpG,CHG and CHH(H=A or T or C),respectively.Besides,101,612 methylation haplotype blocks(MHBs)were identified,including 451 MHBs that were significantly different(dMHB)between the two groups.A total of 2130 differentially expressed(DE)genes(1378 with up‑regulated and 752 with down‑regulated expression)were found in SUG.Integration of methylome and transcriptome data with MethGET program revealed 1623 genes with signifi‑cant changes in their methylation levels and/or gene expression changes(MetGDE genes,MethGET P‑value<0.001).Functional enrichment of genes harboring≥15 DMCs,DE genes and MetGDE genes suggest significant involvement of DNA methylation changes in the regulation of the host immune response to S.uberis infection,especially cytokine activities.Furthermore,discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers,including 6 DE genes,15 CpG‑DMCs and 5 dMHBs that discriminated between SUG and CTG.Conclusion:The integration of methylome and transcriptome of milk somatic cells suggests the possible involve‑ment of DNA methylation changes in the regulation of the host immune response to subclinical mastitis due to S.uberis.The presented genetic and epigenetic biomarkers could contribute to the design of management strategies of subclinical mastitis and breeding for mastitis resistance.

Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma

Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes

●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

DNA methylation as a mediator of epigenetic regulation in the pathogenesis and precision medicine of osteoarthritis:An updated review

The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does not adequately account for all clinical characteristics and heterogeneity of OA.Genetics has emerged as a nascent and crucial area of research in OA.The epigenetic module presents a potential link between genetic and environmental risk factors and the susceptibility and pathogenesis of OA.As a critical epigenetic alteration,DNA methylation has been shown to have an important role in the etiology of OA and is a viable biomarker for predicting disease progression and medication response,as shown in this research.This review aims to update knowledge in the field of DNA methylation associated with OA to better identify the essential features of OA subtypes and pathological conditions,hence accelerating individualized treatment and precision medicine.

DNA hypomethylation promotes learning and memory recovery in a rat model of cerebral ischemia/reperfusion injury

Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.

Revolutionizing Non-Invasive Biomarker Discoveries: The Power of Methylation Screening Analysis in Cell-Free DNA Liquid Biopsy

Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylation patterns for both hypermethylation and hypomethylation lead the way in discovery of novel diagnosis and treatment targets. Many different approaches are present to detect the level of methylation in whole genome (whole genome bisulfite sequencing, microarray) as well as at specific loci (methylation specific PCR). Cell-free DNA (cf-DNA) found in body fluids like blood provides information about DNA methylation and serves as a less invasive approach for genetic screening. Cell-free DNA and methylation screening technologies, when combined, have the potential to transform the way we approach genetic screening and personalized therapy. These technologies can help enhance disease diagnostic accuracy and inform the development of targeted therapeutics by providing a non-invasive way for acquiring genomic information and identifying disease-associated methylation patterns. We highlight the clinical benefits of using cell-free DNA (cf-DNA) liquid biopsy analysis and available methylation screening technologies that have been crucial in identifying biomarkers for disease from patients using a non-invasive way. Powering such biomarker discoveries are various methods of cf-DNA methylation analysis such as Bisulfite Sequencing and most recently, Methylation-Specific Restriction Enzyme (MSRE-seq) Analysis, paving the way for novel epigenetic biomarker discoveries for more robust diagnosis such as early disease detection, prognosis, monitoring of disease progression and treatment response as well as discovery of novel drug targets.

A Metaheuristic Technique for Cluster-Based Feature Selection of DNA Methylation Data for Cancer

Epigenetics is the study of phenotypic variations that do not alter DNA sequences.Cancer epigenetics has grown rapidly over the past few years as epigenetic alterations exist in all human cancers.One of these alterations is DNA methylation;an epigenetic process that regulates gene expression and often occurs at tumor suppressor gene loci in cancer.Therefore,studying this methylation process may shed light on different gene functions that cannot otherwise be interpreted using the changes that occur in DNA sequences.Currently,microarray technologies;such as Illumina Infinium BeadChip assays;are used to study DNA methylation at an extremely large number of varying loci.At each DNA methylation site,a beta value(β)is used to reflect the methylation intensity.Therefore,clustering this data from various types of cancers may lead to the discovery of large partitions that can help objectively classify different types of cancers aswell as identify the relevant loci without user bias.This study proposed a Nested Big Data Clustering Genetic Algorithm(NBDC-GA);a novel evolutionary metaheuristic technique that can perform cluster-based feature selection based on the DNA methylation sites.The efficacy of the NBDC-GA was tested using real-world data sets retrieved from The Cancer Genome Atlas(TCGA);a cancer genomics program created by the NationalCancer Institute(NCI)and the NationalHuman Genome Research Institute.The performance of the NBDC-GA was then compared with that of a recently developed metaheuristic Immuno-Genetic Algorithm(IGA)that was tested using the same data sets.The NBDC-GA outperformed the IGA in terms of convergence performance.Furthermore,the NBDC-GA produced a more robust clustering configuration while simultaneously decreasing the dimensionality of features to a maximumof 67%and of 94.5%for individual cancer type and collective cancer,respectively.The proposed NBDC-GA was also able to identify two chromosomes with highly contrastingDNAmethylations activities that were previously linked to cancer.

Comparative detection of syndecan-2 methylation in preoperative and postoperative stool DNA in patients with colorectal cancer

BACKGROUND Early detection of colorectal cancer(CRC)is essential to reduce cancer-related morbidity and mortality.Stool DNA(sDNA)testing is an emerging method for early CRC detection.Syndecan-2(SDC2)methylation is a potential biomarker for the sDNA testing.Aberrant DNA methylation is an early epigenetic event during tumorigenesis and can occur in the normal colonic mucosa during aging,which can compromise the sDNA test results.METHODS In this prospective study,we enrolled 151 patients with CRC who underwent curative surgical resection between September 2016 and May 2020.Preoperative stool samples were collected from 123 patients and postoperative samples were collected from 122 patients.A total of 104 samples were collected from both preoperative and postoperative patients.Aberrant promoter methylation of SDC2 in sDNA was assessed using linear target enrichment quantitative methylation-specific real-time polymerase chain reaction.Clinicopathological parameters were analyzed using the results of SDC2 methylation.RESULTS Detection rates of SDC2 methylation in the preoperative and postoperative stool samples were 88.6%and 19.7%,respectively.Large tumor size(3 cm,P=0.019)and advanced T stage(T3–T4,P=0.033)were positively associated with the detection rate of SDC2 methylation before surgery.Female sex was associated with false positives after surgery(P=0.030).Cycle threshold(CT)values were significantly decreased postoperatively compared with preoperative values(P<0.001).The postoperative negative conversion rate for preoperatively methylated SDC2 was 79.3%(73/92).CONCLUSION Our results suggested that the SDC2 methylation test for sDNA has acceptable sensitivity and specificity.However,small size and early T stage tumors are associated with a low detection rate of SDC2 methylation.As the cycle threshold values significantly decreased after surgery,SDC2 methylation test for sDNA might have a diagnostic value for CRC.

Stress Treatments and DNA Methylation Affected the Somatic Embryogenesis of Citrus Callus

The evaluation on the callus embryogenesis capacity of 15 genotypes of citrus showed that stress treatments were conducive to somatic embryogenesis and could enhance the recovery of the missed capacity of embryogenesis for some genotypes. Randomly amplified polymorphic DNA (RAPD) and methylation sensitive amplified polymorphism (MSAP) analysis indicated that there existed significant differences in DNA methylation status between the callus capable of producing somatic embryoids and that which missed the embryogenesis capacity of the same genotype Newhall navel orange ( Citrus sinensis Osb. cv. Newhall). The DNA methylation level of the former was lower than that of the latter. However, RAPD profiles did not show any difference between these two kinds of callus.

Eucaryotic DNA Methylation and Gene Mutation

5-methylcytosine (m5C) as a rare base exists in eucaryotic genomes, it is a normal constituent of many eucaryotic DNA, whose existence is a character of eucaryotic DNA. In the regular physiological conditions, cytosine residue of eucaryotic DNA is methylated to be popular. Up to the present, many people consider that the m5C may be mutation hotspots by the m5C deamination leading to gene mutation. Our theoretical investigations indicated that the spontaneous mutation caused by the transition of G - C-A - T, in eukaryotic DNA, may be a result caused by the tautomer changing base pairs and may also be caused by other factor actions, however it could not be caused by the deamination of m5C.

不同运动方式对人体DNA损伤、DNA甲基化和端粒长度的影响

背景:运动不仅是改善身体健康和心理健康的有效手段,还对代谢性和心脑血管等疾病的发生、发展具有良好的干预效果,其原因与表观遗传因素有关。目的:总结不同运动方式对人体DNA损伤、DNA甲基化和端粒长度的影响,并分析运动调控表观遗传修饰的可能机制,以期为运动改善机体功能提供参考。方法:以“运动,有氧训练,急性运动,无氧训练,抗阻训练,DNA损伤,DNA甲基化,端粒”为中文检索词,以“exercise,sport,aerobic exercise,anaerobic exercise,resistance training,acute exercise,DNA methylation,DNA damage,telomere”为英文检索词。在PubMed、Embase、Web of Science、中国知网数据库中进行检索,并根据纳入与排除标准筛选文献,最终纳入70篇文献。结果与结论:①长期有氧、抗阻和无氧运动均能改善DNA损伤,其原因与运动可以提高机体的抗氧化能力有关。而急性运动则会通过上调活性氧和活性氮氧化物的表达进而加剧DNA损伤程度;②急性运动、长期抗阻运动和无氧运动在降低DNA甲基化方面具有积极作用,其关键机制可能是运动诱导的活性氧使氧化型谷胱甘肽/还原型谷胱甘肽比值和DNA甲基化转移酶、10-11易位酶的表达发生了改变,进而对DNA甲基化产生调控作用;③与其他运动形式相比,长时间有氧运动可能更具有增加端粒长度的潜在价值,其中的生物学机制涉及炎症、氧化应激、DNA甲基化和微小RNA的表达调控;④基于当前文献可知,有氧运动持续2年以上可以增加端粒长度,未来的研究也应进一步明确最佳的运动持续时间。