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Wiley Interdisciplinary Reviews. RNA Nov 2021In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding... (Review)
Review
In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding RNA (lncRNAs), exhibit the capability to control posttranslational modifications of nonhistone proteins in both invertebrates and vertebrates. The extent of such a regulation is still largely unknown. We performed a systematic review to identify and evaluate the potential impact of lncRNA-dependent methylation of nonhistone proteins. Collectively, these lncRNAs primarily act as scaffolds upon which methyltransferases (MTases) and targets are brought in proximity. In this manner, the N-MTase activity of EZH2, protein arginine-MTase 1/4/5, and SMYD2 is exploited to modulate the stability or the compartmentalization of several nonhistone proteins with roles in cell signaling, gene expression, and RNA processing. Moreover, these lncRNAs can indirectly affect the methylation of nonhistone proteins by transcriptional or posttranscriptional regulation of MTases. Strikingly, the lncRNAs/MTases/nonhistone proteins networking seem to be relevant to carcinogenesis and neurological disorders. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
Topics: Animals; Gene Expression Regulation; Methylation; Protein Processing, Post-Translational; RNA Processing, Post-Transcriptional; RNA, Long Noncoding
PubMed: 33913612
DOI: 10.1002/wrna.1661 -
Human Reproduction Update Nov 2020Studies in non-human mammals suggest that environmental factors can influence spermatozoal DNA methylation, and some research suggests that spermatozoal DNA methylation...
BACKGROUND
Studies in non-human mammals suggest that environmental factors can influence spermatozoal DNA methylation, and some research suggests that spermatozoal DNA methylation is also implicated in conditions such as subfertility and imprinting disorders in the offspring. Together with an increased availability of cost-effective methods of interrogating DNA methylation, this premise has led to an increasing number of studies investigating the DNA methylation landscape of human spermatozoa. However, how the human spermatozoal DNA methylome is influenced by environmental factors is still unclear, as is the role of human spermatozoal DNA methylation in subfertility and in influencing offspring health.
OBJECTIVE AND RATIONALE
The aim of this systematic review was to critically appraise the quality of the current body of literature on DNA methylation in human spermatozoa, summarize current knowledge and generate recommendations for future research.
SEARCH METHODS
A comprehensive literature search of the PubMed, Web of Science and Cochrane Library databases was conducted using the search terms 'semen' OR 'sperm' AND 'DNA methylation'. Publications from 1 January 2003 to 2 March 2020 that studied human sperm and were written in English were included. Studies that used sperm DNA methylation to develop methodologies or forensically identify semen were excluded, as were reviews, commentaries, meta-analyses or editorial texts. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria were used to objectively evaluate quality of evidence in each included publication.
OUTCOMES
The search identified 446 records, of which 135 were included in the systematic review. These 135 studies were divided into three groups according to area of research; 56 studies investigated the influence of spermatozoal DNA methylation on male fertility and abnormal semen parameters, 20 studies investigated spermatozoal DNA methylation in pregnancy outcomes including offspring health and 59 studies assessed the influence of environmental factors on spermatozoal DNA methylation. Findings from studies that scored as 'high' and 'moderate' quality of evidence according to GRADE criteria were summarized. We found that male subfertility and abnormal semen parameters, in particular oligozoospermia, appear to be associated with abnormal spermatozoal DNA methylation of imprinted regions. However, no specific DNA methylation signature of either subfertility or abnormal semen parameters has been convincingly replicated in genome-scale, unbiased analyses. Furthermore, although findings require independent replication, current evidence suggests that the spermatozoal DNA methylome is influenced by cigarette smoking, advanced age and environmental pollutants. Importantly however, from a clinical point of view, there is no convincing evidence that changes in spermatozoal DNA methylation influence pregnancy outcomes or offspring health.
WIDER IMPLICATIONS
Although it appears that the human sperm DNA methylome can be influenced by certain environmental and physiological traits, no findings have been robustly replicated between studies. We have generated a set of recommendations that would enhance the reliability and robustness of findings of future analyses of the human sperm methylome. Such studies will likely require multicentre collaborations to reach appropriate sample sizes, and should incorporate phenotype data in more complex statistical models.
Topics: DNA Methylation; Female; Humans; Infertility, Male; Male; Pregnancy; Pregnancy Outcome; Reproducibility of Results; Semen; Spermatozoa
PubMed: 32790874
DOI: 10.1093/humupd/dmaa025 -
Cell Death Discovery Apr 2024Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and... (Review)
Review
Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and therapeutic tools are limited. Thus, identifying new targets for the diagnosis and treatment of corneal diseases has gained great interest. Methylation, a type of epigenetic modification, modulates various cellular processes at both nucleic acid and protein levels. Growing evidence shows that methylation is a key regulator in the pathogenesis of corneal diseases, including inflammation, fibrosis, and neovascularization, making it an attractive potential therapeutic target. In this review, we discuss the major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases. Also, we provide insights into identifying potential biomarkers of methylation that may improve the diagnosis and treatment of corneal diseases.
PubMed: 38589350
DOI: 10.1038/s41420-024-01935-2 -
Heliyon Oct 2022DNA methylation is an effective epigenetic process that is frequently linked to changes in gene expression. Zinc is a vital micronutrient that plays a crucial role in...
BACKGROUND
DNA methylation is an effective epigenetic process that is frequently linked to changes in gene expression. Zinc is a vital micronutrient that plays a crucial role in DNA methylation. Therefore, abnormal zinc levels may cause aberrant DNA methylation and other diseases.
OBJECTIVES
To investigate the influence of zinc on gene-specific and global DNA methylation in humans and rodents, their tissues and their cells.
METHOD
Systematic literature searches were conducted using Medline, Scopus, Google Scholar, and Web of Science databases. Studies that met the inclusion criteria and were published in English language were included. Data including the first author, sample size, subjects, targeted genes, tissue types or cells analysed, zinc level, molecular techniques, DNA methylation outcomes, and consequences were extracted.
RESULTS
From a total of 2360 articles screened by title and abstract, 15 met the inclusion criteria. Qualitative analysis indicates that there are associations between zinc deficiency and gene-specific hypomethylation in humans and between zinc deficiency and hypermethylation in rodents. Zinc did not influence LINE-1 methylation in humans. Depending on cell type, zinc could have a positive or negative effect on global methylation in humans and rodents. As predicted, in general, gene expression was elevated by DNA hypomethylation and the corresponding protein levels were also upregulated. However, some studies showed that zinc deficiency led to reduced gene expression or no alteration in mRNA levels and corresponding protein levels.
CONCLUSION
Our study shows links between zinc levels and DNA methylation. However, greater significance may be achieved if more than one independent investigator analyses the same set of genes in the same cell type. Therefore, gene-cell and animal-specific investigations are recommended to reduce variability and allow comparisons across studies.
PubMed: 36203899
DOI: 10.1016/j.heliyon.2022.e10815 -
Pharmacotherapy Apr 2020The pharmacoepigenetics of antipsychotic treatment in severe mental illness is a growing area of research that aims to understand the interface between antipsychotic...
The pharmacoepigenetics of antipsychotic treatment in severe mental illness is a growing area of research that aims to understand the interface between antipsychotic treatment and genetic regulation. Pharmacoepigenetics may some day assist in identifying treatment response mechanisms or become one of the components in the implementation of precision medicine. To understand the current evidence regarding the effects of antipsychotics on DNA methylation a systematic review with qualitative synthesis was performed through Pubmed, Embase and Psychinfo from earliest data to June 2019. Studies were included if they analyzed DNA methylation in an antipsychotic-treated population of patients with schizophrenia or bipolar disorder. Data extraction occurred via a standardized format and study quality was assessed. Twenty-nine studies were identified for inclusion. Study design, antipsychotic type, sample source, and methods of DNA methylation measurement varied across all studies. Eighteen studies analyzed methylation in patients with schizophrenia, four studies in patients with bipolar disorder, and seven studies in a combined sample of schizophrenia and bipolar disorder. Twenty-two studies used observational samples whereas the remainder used prospectively treated samples. Six studies assessed global methylation, five assessed epigenome-wide, and 15 performed a candidate epigenetic study. Two studies analyzed both global and gene-specific methylation, whereas one study performed a simultaneous epigenome-wide and gene-specific study. Only three genes were analyzed in more than one gene-specific study and the findings were discordant. The state of the pharmacoepigenetic literature on antipsychotic use is still in its early stages and uniform reporting of methylation site information is needed. Future work should concentrate on using prospective sampling with appropriate control groups and begin to replicate many of the novel associations that have been reported.
Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Schizophrenia
PubMed: 32058614
DOI: 10.1002/phar.2375 -
Briefings in Functional Genomics Jul 2020Coronary artery disease (CAD) and ischemic stroke are the two most predominant forms of cardiovascular diseases (CVDs) caused by genetic, epigenetic and environmental...
Coronary artery disease (CAD) and ischemic stroke are the two most predominant forms of cardiovascular diseases (CVDs) caused by genetic, epigenetic and environmental risk factors. Although studies on the impact of 'epigenetics' in CVDs is not new, its effects are increasingly being realized as a key regulatory determinant that may drive predisposition, pathophysiology and therapeutic outcome. The most widely studied epigenetic risk factors are regulated by DNA methylation and miRNA expression. To keep pace with growing developments and discoveries, a comprehensive review was performed using Pubmed, Science Direct and Scopus databases to highlight the role of DNA methylation and miRNAs in CAD and stroke subjects. Network analysis was performed using ClueGO software and miRTargetLink database. We identified 32 studies of DNA methylation on CAD and stroke, of which, 6 studies showed differences in global DNA methylation, 10 studies reported the genome-wide difference in DNA methylation and 16 studies demonstrated altered DNA methylation at 14 candidate loci. The network analysis showed positive regulation of nitric oxide biosynthetic process, homocysteine metabolic process and negative regulation of lipid storage. About, 155 miRNAs were associated with CAD, stroke and related phenotypes in 83 studies. Interestingly, mir-223 hypomethylation and altered expression were associated with cerebral infarction and stroke. The target prediction for 18 common miRNAs between CAD and stroke showed strong interaction with SP3 and SP1 genes. This systematic review addresses the present knowledge on DNA methylation and miRNAs in CAD and stroke, whose abnormal regulation has been implicated in etiology or progression of the diseases.
Topics: Cardiovascular Diseases; Coronary Artery Disease; DNA Methylation; Databases, Factual; Databases, Genetic; Genome-Wide Association Study; Homocysteine; Humans; Lipid Metabolism; MicroRNAs; Nitric Oxide; Stroke
PubMed: 31950130
DOI: 10.1093/bfgp/elz043 -
Archives of Gynecology and Obstetrics Feb 2024Polycystic ovary syndrome (PCOS) is an endocrine metabolic disease that affects women of reproductive age and is one of the main causes of anovulatory infertility.... (Review)
Review
PURPOSE
Polycystic ovary syndrome (PCOS) is an endocrine metabolic disease that affects women of reproductive age and is one of the main causes of anovulatory infertility. However, the cause of PCOS is yet fully understood, and genetic factors play an important role in its etiology. In this study, we reviewed the main genes involved in the etiology of PCOS and the influence of DNA methylation, aiming to answer the study´s guiding question: 'What is the influence of DNA methylation on the main genes involved in PCOS?'.
METHODS
We used the MEDLINE database, and inclusion criteria (primary and original articles, written in English, found through our entry terms) and exclusion criteria (literature reviews and articles that used animals to perform the experiments and that focused in other epigenetics mechanism without being DNA methylation) were applied.
RESULTS
Twenty-three scientific articles, from a total of 43 articles read in full, were chosen for this study. Eighteen studies confirmed DNA methylation associated with PCOS.
CONCLUSION
The most relevant genes related to PCOS were INSR, LHCGR, and RAB5B, which may be epigenetically altered in DNA, with the first two genes hypomethylated and the last hypermethylated. The epigenetic changes presented in the genes related to PCOS or their promoters were only at the CpG sites.
Topics: Animals; Female; Humans; DNA Methylation; Polycystic Ovary Syndrome; Epigenesis, Genetic; Reproduction
PubMed: 37119419
DOI: 10.1007/s00404-023-07025-5 -
Clinical Epigenetics Feb 2022Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications....
BACKGROUND
Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant complications, such as allograft rejection, chronic renal allograft dysfunction, and cutaneous squamous cell carcinoma, have a suboptimal predictive value. DNA methylation is an epigenetic modification that directly affects gene expression and plays an important role in processes such as ischemia/reperfusion injury, fibrosis, and alloreactive immune response. Novel techniques can quickly assess the DNA methylation status of multiple loci in different cell types, allowing a deep and interesting study of cells' activity and function. Therefore, DNA methylation has the potential to become an important biomarker for prediction and monitoring in kidney transplantation.
PURPOSE OF THE STUDY
The aim of this study was to evaluate the role of DNA methylation as a potential biomarker of graft survival and complications development in kidney transplantation. MATERIAL AND METHODS: A systematic review of several databases has been conducted. The Newcastle-Ottawa scale and the Jadad scale have been used to assess the risk of bias for observational and randomized studies, respectively.
RESULTS
Twenty articles reporting on DNA methylation as a biomarker for kidney transplantation were included, all using DNA methylation for prediction and monitoring. DNA methylation pattern alterations in cells isolated from different tissues, such as kidney biopsies, urine, and blood, have been associated with ischemia-reperfusion injury and chronic renal allograft dysfunction. These alterations occurred in different and specific loci. DNA methylation status has also proved to be important for immune response modulation, having a crucial role in regulatory T cell definition and activity. Research also focused on a better understanding of the role of this epigenetic modification assessment for regulatory T cells isolation and expansion for future tolerance induction-oriented therapies.
CONCLUSIONS
Studies included in this review are heterogeneous in study design, biological samples, and outcome. More coordinated investigations are needed to affirm DNA methylation as a clinically relevant biomarker important for prevention, monitoring, and intervention.
Topics: Biomarkers; DNA Methylation; Graft Rejection; Humans; Kidney Neoplasms; Kidney Transplantation; Risk Assessment
PubMed: 35130936
DOI: 10.1186/s13148-022-01241-7 -
Anticancer Research Apr 2020Several studies have investigated the influence of obesity on DNA methylation (DNAm) to find biomarkers associated with the detection of chronic diseases, including... (Review)
Review
BACKGROUND/AIM
Several studies have investigated the influence of obesity on DNA methylation (DNAm) to find biomarkers associated with the detection of chronic diseases, including breast cancer. The aim of the study was to systematically review studies examining the association of body mass index (BMI) and DNAm in blood or normal breast tissue.
MATERIALS AND METHODS
Three scientific literature databases (PubMed, Embase and Web of Science) were screened until May 2018.
RESULTS
Twenty-four studies were included along with ours in which we investigated this relation in the normal breast tissue of 40 breast cancer patients.
CONCLUSION
BMI-associated CpG sites were highly variable with few identified in less than half of the studies. Nevertheless, a few genes potentially associated with BMI were highlighted in blood (CPT1A, ABCG1, SREBF1 and LGALS3BP) and in normal breast tissue (PTPRN2 and ABLIM2). The variability of the results could be explained by the tissue and cell-specificity of methylation and differences in methodology.
Topics: Biomarkers, Tumor; Body Mass Index; Breast; Breast Neoplasms; CpG Islands; DNA Methylation; Epigenesis, Genetic; Female; Humans; Obesity
PubMed: 32234868
DOI: 10.21873/anticanres.14134 -
Neurosurgical Review Apr 2024Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after... (Review)
Review
Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.
Topics: Humans; Subarachnoid Hemorrhage; DNA Methylation; Cerebral Infarction; Brain Ischemia; Biomarkers; Vasospasm, Intracranial; Cadherin Related Proteins
PubMed: 38594575
DOI: 10.1007/s10143-024-02381-5