scholarly journals DNA Methylation in Genetic and Sporadic Forms of Neurodegeneration: Lessons From Alzheimers, Related Tauopathies and Genetic Tauopathies

2021 ◽  
Author(s):  
Geraldine Zimmer-Bensch ◽  
Hans Zempel
Keyword(s):  
Dna Methylation ◽  
Current Knowledge ◽  
Ectopic Expression ◽  
Premature Death ◽  
Epigenetic Mechanism ◽  
Neurological Deficits ◽  
Epigenetic Therapy ◽  
Disease Etiology ◽  
Mapt Gene ◽  
Epigenetic Signatures

Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer’s Disease, are a scourge of the aging society, and in case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and/ or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here we review current knowledge of tauopathies listing known genetic and important sporadic forms of this disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer’s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tool and usage of epigenetic therapy strategies for these diseases.

scholarly journals DNA Methylation in Genetic and Sporadic Forms of Neurodegeneration: Lessons from Alzheimer’s, Related Tauopathies and Genetic Tauopathies

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3064
Author(s):  
Geraldine Zimmer-Bensch ◽  
Hans Zempel
Keyword(s):  
Dna Methylation ◽  
Current Knowledge ◽  
Ectopic Expression ◽  
Premature Death ◽  
Epigenetic Mechanism ◽  
Neurological Deficits ◽  
Diagnostic Tools ◽  
Epigenetic Therapy ◽  
Disease Etiology ◽  
Mapt Gene

Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer’s Disease, are a scourge of the aging society, and in the case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and/or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here, we review current knowledge of tauopathies listing known genetic and important sporadic forms of these disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer’s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tools and usages of epigenetic therapy strategies for these diseases.

scholarly journals DNA methylation in thyroid cancer

2019 ◽  
Vol 26 (7) ◽  
pp. R415-R439 ◽  
Author(s):  
Carles Zafon ◽  
Joan Gil ◽  
Beatriz Pérez-González ◽  
Mireia Jordà
Keyword(s):  
Dna Methylation ◽  
Thyroid Cancer ◽  
Cancer Genomics ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
Epigenetic Mechanism ◽  
Aberrant Methylation ◽  
Technological Advances ◽  
Molecular Landscape

In recent years, cancer genomics has provided new insights into genetic alterations and signaling pathways involved in thyroid cancer. However, the picture of the molecular landscape is not yet complete. DNA methylation, the most widely studied epigenetic mechanism, is altered in thyroid cancer. Recent technological advances have allowed the identification of novel differentially methylated regions, methylation signatures and potential biomarkers. However, despite recent progress in cataloging methylation alterations in thyroid cancer, many questions remain unanswered. The aim of this review is to comprehensively examine the current knowledge on DNA methylation in thyroid cancer and discuss its potential clinical applications. After providing a general overview of DNA methylation and its dysregulation in cancer, we carefully describe the aberrant methylation changes in thyroid cancer and relate them to methylation patterns, global hypomethylation and gene-specific alterations. We hope this review helps to accelerate the use of the diagnostic, prognostic and therapeutic potential of DNA methylation for the benefit of thyroid cancer patients.

scholarly journals Epigenetic Basis of Molecular Changes in Animal Cells with Particular Regard to Embryonic Development – A Review / Epigenetyczne Podstawy Przemian Molekularnych Zachodzących W Komórkach Zwierzęcych, Ze Szczególnym Uwzględnieniem Rozwoju Embrionalnego – Artykuł Przeglądowy

2013 ◽  
Vol 13 (4) ◽  
pp. 675-685
Author(s):  
Joanna Romanek
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Embryonic Development ◽  
De Novo ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Epigenetic Mechanism ◽  
Animal Cells ◽  
Molecular Changes ◽  
De Novo Methylation

Abstract Regulation of gene expression is a complex process. Epigenetics is the study of heritable changes in gene expression independently of DNA sequence. Epigenetic control of gene transcription is based on two main processes. The first is reversible DNA methylation, primarily of cytosine at position C5, rarely in position N3, or of adenine at position C6 (Xu et al., 2010). The second process is the change in chromatin structure and function by chemical modification of histones, including mainly methylation, acetylation, and phosphorylation of histone amino acids (Zamudio et al., 2008). During development and differentiation of cells, changes occur in DNA methylation of genes. After fertilization there are dynamic histone modifications and changes in DNA methylation in zygotes. Use of methylation sensitive restriction enzymes causes a global demethylation in the early embryonic stage (Sulewska et al., 2007 b). De novo methylation of CpG sites is followed by embryo implantation. Next, during gastrulation most genes are methylated except the tissue-specific genes. The last wave of de novo methylation takes place during the gametogenesis and is dependent on sex (Sulewska et al., 2007 b). The aim of this work is to review the current knowledge about epigenetic mechanism of molecular changes in animal cells with particular regard to embryonic development.

scholarly journals Distinct epigenetic signatures between adult-onset and late-onset depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hirotaka Yamagata ◽  
Hiroyuki Ogihara ◽  
Koji Matsuo ◽  
Shusaku Uchida ◽  
Ayumi Kobayashi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Adult Onset ◽  
Blood Biomarkers ◽  
Major Depressive ◽  
Genome Wide ◽  
Healthy Control ◽  
Epigenetic Signatures

AbstractThe heterogeneity of major depressive disorder (MDD) is attributed to the fact that diagnostic criteria (e.g., DSM-5) are only based on clinical symptoms. The discovery of blood biomarkers has the potential to change the diagnosis of MDD. The purpose of this study was to identify blood biomarkers of DNA methylation by strategically subtyping patients with MDD by onset age. We analyzed genome-wide DNA methylation of patients with adult-onset depression (AOD; age ≥ 50 years, age at depression onset < 50 years; N = 10) and late-onset depression (LOD; age ≥ 50 years, age at depression onset ≥ 50 years; N = 25) in comparison to that of 30 healthy subjects. The methylation profile of the AOD group was not only different from that of the LOD group but also more homogenous. Six identified methylation CpG sites were validated by pyrosequencing and amplicon bisulfite sequencing as potential markers for AOD in a second set of independent patients with AOD and healthy control subjects (N = 11). The combination of three specific methylation markers achieved the highest accuracy (sensitivity, 64%; specificity, 91%; accuracy, 77%). Taken together, our findings suggest that DNA methylation markers are more suitable for AOD than for LOD patients.

scholarly journals Salivary DNA Methylation as an Epigenetic Biomarker for Head and Neck Cancer. Part I: A Diagnostic Accuracy Meta-Analysis

2021 ◽  
Vol 11 (6) ◽  
pp. 568
Author(s):  
Óscar Rapado-González ◽  
Cristina Martínez-Reglero ◽  
Ángel Salgado-Barreira ◽  
Laura Muinelo-Romay ◽  
Juan Muinelo-Lorenzo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Head And Neck Cancer ◽  
Diagnostic Accuracy ◽  
Head And Neck ◽  
Likelihood Ratio ◽  
Neck Cancer ◽  
Meta Analysis ◽  
Positive Likelihood Ratio ◽  
Epigenetic Mechanism ◽  
Cochrane Library

DNA hypermethylation is an important epigenetic mechanism for gene expression inactivation in head and neck cancer (HNC). Saliva has emerged as a novel liquid biopsy representing a potential source of biomarkers. We performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of salivary DNA methylation for detecting HNC. PubMed EMBASE, Web of Science, LILACS, and the Cochrane Library were searched. Study quality was assessed by the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (dOR), and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess heterogeneity. Eighty-four study units from 18 articles with 8368 subjects were included. The pooled sensitivity and specificity of salivary DNA methylation were 0.39 and 0.87, respectively, while PLR and NLR were 3.68 and 0.63, respectively. The overall area under the curve (AUC) was 0.81 and the dOR was 8.34. The combination of methylated genes showed higher diagnostic accuracy (AUC, 0.92 and dOR, 36.97) than individual gene analysis (AUC, 0.77 and dOR, 6.02). These findings provide evidence regarding the potential clinical application of salivary DNA methylation for HNC diagnosis.

scholarly journals Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children

2020 ◽  
pp. 1-11
Author(s):  
Lorenza Dall’ Aglio ◽  
Jolien Rijlaarsdam ◽  
Rosa H. Mulder ◽  
Alexander Neumann ◽  
Janine F. Felix ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stress Responses ◽  
Association Studies ◽  
Maternal Sensitivity ◽  
Population Based ◽  
Epigenetic Mechanism ◽  
Developmental Problems ◽  
Maternal Caregiving ◽  
Typical Variation

Abstract Background Experimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment. Methods Here, we explored the prospective association between typical variation in maternal sensitivity and offspring epigenome-wide DNAm, in a population-based cohort of children (N = 235). Maternal sensitivity was observed when children were 3- and 4-years-old. DNAm, quantified with the Infinium 450 K array, was extracted at age 6 (whole blood). The influence of methylation quantitative trait loci (mQTLs), DNAm at birth (cord blood), and confounders (socioeconomic status, maternal psychopathology) was considered in follow-up analyses. Results Genome-wide significant associations between maternal sensitivity and offspring DNAm were observed at 13 regions (p < 1.06 × 10−07), but not at single sites. Follow-up analyses indicated that associations at these regions were in part related to genetic factors, confounders, and baseline DNAm levels at birth, as evidenced by the presence of mQTLs at five regions and estimate attenuations. Robust associations with maternal sensitivity were found at four regions, annotated to ZBTB22, TAPBP, ZBTB12, and DOCK4. Conclusions These findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses.

scholarly journals Disease-associated DNA methylation signatures in esophageal biopsies of children diagnosed with Eosinophilic Esophagitis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Caterina Strisciuglio ◽  
Felicity Payne ◽  
Komal Nayak ◽  
Marialuisa Andreozzi ◽  
Alessandra Vitale ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Eosinophilic Esophagitis ◽  
Field Potential ◽  
Line Treatment ◽  
Food Impaction ◽  
First Line ◽  
Genome Wide ◽  
Epigenetic Signatures ◽  
The Impact ◽  
First Line Treatment

AbstractEosinophilic esophagitis (EoE) is a leading cause of dysphagia and food impaction in children and adults. The diagnosis relies on histological examination of esophageal mucosal biopsies and requires the presence of > 15 eosinophils per high-powered field. Potential pitfalls include the impact of biopsy sectioning as well as regional variations of eosinophil density. We performed genome-wide DNA methylation analyses on 30 esophageal biopsies obtained from children diagnosed with EoE (n = 7) and matched controls (n = 13) at the time of diagnosis as well as following first-line treatment. Analyses revealed striking disease-associated differences in mucosal DNA methylation profiles in children diagnosed with EoE, highlighting the potential for these epigenetic signatures to be developed into clinically applicable biomarkers.

scholarly journals Global DNA methylation was changed by a maternal high-lipid, high-energy diet during gestation and lactation in male adult mice liver

2015 ◽  
Vol 113 (7) ◽  
pp. 1032-1039 ◽  
Author(s):  
Huan-Ling Yu ◽  
Shan Dong ◽  
Li-Fang Gao ◽  
Li Li ◽  
Yuan-Di Xi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Maternal Diet ◽  
High Energy ◽  
Methylation Pattern ◽  
Epigenetic Mechanism ◽  
Chow Diet ◽  
Mrna Levels ◽  
Promoter Regions ◽  
Male Adult ◽  
High Lipid

An epigenetic mechanism has been suggested to explain the effects of the maternal diet on the development of disease in offspring. The present study aimed to observe the effects of a maternal high-lipid, high-energy (HLE) diet on the DNA methylation pattern of male offspring in mice. Female C57BL/6J mice were fed an HLE diet during gestation and lactation. The genomic DNA methylations at promoter sites of genes in the liver, mRNA and protein levels of selected genes related to lipid and glucose metabolism were measured by microarray, real-time PCR and Western blot. The results indicated that the percentage of methylated DNA in offspring from dams that were fed an HLE diet was significantly higher than that from dams that were fed a chow diet, and most of these genes were hypermethylated in promoter regions. The nuclear protein content and mRNA levels of hypermethylated genes, such as PPARγ and liver X receptor α (LXRα), were decreased significantly in offspring in the HLE group. The results suggested that the DNA methylation profile in adult offspring livers was changed by the maternal HLE diet during gestation and lactation.

scholarly journals Deciphering DNA Methylation in HIV Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Thilona Arumugam ◽  
Upasana Ramphal ◽  
Theolan Adimulam ◽  
Romona Chinniah ◽  
Veron Ramsuran
Keyword(s):  
Dna Methylation ◽  
Hiv Infection ◽  
Therapeutic Strategy ◽  
New Drugs ◽  
Sub Saharan Africa ◽  
Epigenetic Mechanism ◽  
People Living With Hiv ◽  
Modifying Factors ◽  
Autoimmune Conditions ◽  
Sub Saharan

With approximately 38 million people living with HIV/AIDS globally, and a further 1.5 million new global infections per year, it is imperative that we advance our understanding of all factors contributing to HIV infection. While most studies have focused on the influence of host genetic factors on HIV pathogenesis, epigenetic factors are gaining attention. Epigenetics involves alterations in gene expression without altering the DNA sequence. DNA methylation is a critical epigenetic mechanism that influences both viral and host factors. This review has five focal points, which examines (i) fluctuations in the expression of methylation modifying factors upon HIV infection (ii) the effect of DNA methylation on HIV viral genes and (iii) host genome (iv) inferences from other infectious and non-communicable diseases, we provide a list of HIV-associated host genes that are regulated by methylation in other disease models (v) the potential of DNA methylation as an epi-therapeutic strategy and biomarker. DNA methylation has also been shown to serve as a robust therapeutic strategy and precision medicine biomarker against diseases such as cancer and autoimmune conditions. Despite new drugs being discovered for HIV, drug resistance is a problem in high disease burden settings such as Sub-Saharan Africa. Furthermore, genetic therapies that are under investigation are irreversible and may have off target effects. Alternative therapies that are nongenetic are essential. In this review, we discuss the potential role of DNA methylation as a novel therapeutic intervention against HIV.

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