scholarly journals An epigenetic mechanism for cavefish eye degeneration

2017 ◽  
Author(s):  
Aniket V. Gore ◽  
Kelly A. Tomins ◽  
James Iben ◽  
Li Ma ◽  
Daniel Castranova ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Eye Development ◽  
Phenotypic Diversity ◽  
Phenotypic Variability ◽  
Epigenetic Mechanism ◽  
Gene Repression ◽  
Specific Gene ◽  
Astyanax Mexicanus ◽  
Eye Disorders ◽  
Blind Cave

Coding and non-coding mutations in DNA contribute significantly to phenotypic variability during evolution. However, less is known about the role of epigenetics in this process. Although previous studies have identified eye development genes associated with the loss of eyes phenotype in the Pachón blind cave morph of the Mexican tetra Astyanax mexicanus1-6, no inactivating mutations have been found in any of these genes2,3,7-10. Here we show that excess DNA methylation-based epigenetic silencing promotes eye degeneration in blind cave Astyanax mexicanus. By performing parallel analyses in Astyanax mexicanus cave and surface morphs and in the zebrafish Danio rerio, we have discovered that DNA methylation mediates eye-specific gene repression and globally regulates early eye development. The most significantly hypermethylated and down-regulated genes in the cave morph are also linked to human eye disorders, suggesting the function of these genes is conserved across the vertebrates. Our results show that changes in DNA methylation-based gene repression can serve as an important molecular mechanism generating phenotypic diversity during development and evolution.

scholarly journals Evolutionary History of DNA Methylation Related Genes in Bivalvia: New Insights From Mytilus galloprovincialis

2021 ◽  
Vol 9 ◽  
Author(s):  
Marco Gerdol ◽  
Claudia La Vecchia ◽  
Maria Strazzullo ◽  
Pasquale De Luca ◽  
Stefania Gorbi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mytilus Galloprovincialis ◽  
Adult Life ◽  
Dna Methyltransferases ◽  
Methylation Pattern ◽  
Epigenetic Mechanism ◽  
Specific Gene ◽  
Fundamental Information ◽  
Genome Activity

DNA methylation is an essential epigenetic mechanism influencing gene expression in all organisms. In metazoans, the pattern of DNA methylation changes during embryogenesis and adult life. Consequently, differentiated cells develop a stable and unique DNA methylation pattern that finely regulates mRNA transcription during development and determines tissue-specific gene expression. Currently, DNA methylation remains poorly investigated in mollusks and completely unexplored in Mytilus galloprovincialis. To shed light on this process in this ecologically and economically important bivalve, we screened its genome, detecting sequences homologous to DNA methyltransferases (DNMTs), methyl-CpG-binding domain (MBD) proteins and Ten-eleven translocation methylcytosine dioxygenase (TET) previously described in other organisms. We characterized the gene architecture and protein domains of the mussel sequences and studied their phylogenetic relationships with the ortholog sequences from other bivalve species. We then comparatively investigated their expression levels across different adult tissues in mussel and other bivalves, using previously published transcriptome datasets. This study provides the first insights on DNA methylation regulators in M. galloprovincialis, which may provide fundamental information to better understand the complex role played by this mechanism in regulating genome activity in bivalves.

scholarly journals Gliomas display distinct sex-based differential methylation patterns based on molecular subtype

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Mette L Johansen ◽  
L C Stetson ◽  
Vachan Vadmal ◽  
Kristin Waite ◽  
Michael E Berens ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Subtype ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Epigenetic Mechanism ◽  
Specific Gene ◽  
Lower Grade ◽  
Gene Promoters ◽  
Motif Analysis ◽  
Binding Motifs

Abstract Background Gliomas are the most common type of primary brain tumor and one of many cancers where males are diagnosed with greater frequency than females. However, little is known about the sex-based molecular differences in glioblastomas (GBMs) or lower grade glioma (non-GBM) subtypes. DNA methylation is an epigenetic mechanism involved in regulating gene transcription. In glioma and other cancers, hypermethylation of specific gene promoters downregulates transcription and may have a profound effect on patient outcome. The purpose of this study was to determine if sex-based methylation differences exist in different glioma subtypes. Methods Molecular and clinical data from glioma patients were obtained from The Cancer Genome Atlas and grouped according to tumor grade and molecular subtype (IDH1/2 mutation and 1p/19q chromosomal deletion). Sex-specific differentially methylated probes (DMPs) were identified in each subtype and further analyzed to determine if they were part of differentially methylated regions (DMRs) or associated with differentially methylated DNA transcription regulatory binding motifs. Results Analysis of methylation data in 4 glioma subtypes revealed unique sets of both sex-specific DMPs and DMRs in each subtype. Motif analysis based on DMP position also identified distinct sex-based sets of DNA-binding motifs that varied according to glioma subtype. Downstream targets of 2 of the GBM-specific transcription binding sites, NFAT5 and KLF6, showed differential gene expression consistent with increased methylation mediating downregulation. Conclusion DNA methylation differences between males and females in 4 glioma molecular subtypes suggest an important, sex-specific role for DNA methylation in epigenetic regulation of gliomagenesis.

scholarly journals On the Use of Blood Samples for Measuring DNA Methylation in Ecological Epigenetic Studies

2020 ◽  
Vol 60 (6) ◽  
pp. 1558-1566 ◽  
Author(s):  
Arild Husby
Keyword(s):  
Dna Methylation ◽  
Phenotypic Variation ◽  
Evolutionary Biology ◽  
Phenotypic Diversity ◽  
Genomic Region ◽  
Epigenetic Mechanism ◽  
Blood Samples ◽  
Reduced Representation ◽  
Bisulfite Treatment ◽  
Methylation Patterns

Synopsis There is increasing interest in understanding the potential for epigenetic factors to contribute to phenotypic diversity in evolutionary biology. One well studied epigenetic mechanism is DNA methylation, the addition of a methyl group to cytosines, which have the potential to alter gene expression depending on the genomic region in which it takes place. Obtaining information about DNA methylation at genome-wide scale has become straightforward with the use of bisulfite treatment in combination with reduced representation or whole-genome sequencing. While it is well recognized that methylation is tissue specific, a frequent limitation for many studies is that sampling-specific tissues may require sacrificing individuals, something which is generally undesirable and sometimes impossible. Instead, information about DNA methylation patterns in the blood is frequently used as a proxy tissue. This can obviously be problematic if methylation patterns in the blood do not reflect that in the relevant tissue. Understanding how, or if, DNA methylation in blood reflect DNA methylation patterns in other tissues is therefore of utmost importance if we are to make inferences about how observed differences in methylation or temporal changes in methylation can contribute to phenotypic variation. The aim of this review is to examine what we know about the potential for using blood samples in ecological epigenetic studies. I briefly outline some methods by which we can measure DNA methylation before I examine studies that have compared DNA methylation patterns across different tissues and, finally, examine how useful blood samples may be for ecological studies of DNA methylation. Ecological epigenetic studies are in their infancy, but it is paramount for the field to move forward to have detailed information about tissue and time dependence relationships in methylation to gain insights into if blood DNA methylation patterns can be a reliable bioindicator for changes in methylation that generate phenotypic variation in ecologically important traits.

scholarly journals Genotypic and phenotypic characterization of Streptococcus mutans strains isolated from patients with dental caries

2021 ◽  
Author(s):  
Mohammad Shahadat Hossain ◽  
Sadab Alam ◽  
Yead Morshed Nibir ◽  
Tahrima Arman Tusty ◽  
Sayyeed Mahmud Bulbul ◽  
...  
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Acid Production ◽  
Phenotypic Diversity ◽  
Phenotypic Variability ◽  
Clinical Isolates ◽  
Phenotypic Characterization ◽  
Specific Gene ◽  
Polymerase Chain

Background and Objectives: The oral cavity harbors numerous Streptococcus mutans strains which display remarkable genotypic and phenotypic diversity. This study evaluated the genotypic and phenotypic diversity of 209 S. mutans strains isolated from 336 patients with dental caries and compared with the universal reference strain, UA159. Materials and Methods: Selective cultivation on mitis-salivaries-bacitracin agar and species-specific polymerase chain re- action (PCR) was carried out to isolate and identify the 209 S. mutans isolates from 336 patients with dental caries. Arbitrari- ly primed polymerase chain reaction (AP-PCR), PCR amplification of specific gene, acid production and biofilm formation capacity were performed to evaluate the genotypic and phenotypic variation. Student’s t-test and Chi-square test were used for analysis of variables and a probability (P) of <0.05 was considered as significant. Results: Our study revealed a high degree of genotypic and phenotypic variability among the clinical strains. We observed significant differences in colony morphology, generation time, biofilm formation, and acid production while growing in cul- ture medium. All the clinical isolates were able to lower pH while growing in Todd-Hewitt broth. Consistent with phenotypic variations, we also observed genotypic variation by AP-PCR and gene specific PCR. AP-PCR analysis suggested that most of the patients with dental caries have distinct type of S. mutans strains. Genes related to various two component systems were highly conserved among the isolated strains, however, bacteriocin encoding genes such as nlmAB, nlmC were absent in nearly half of the clinical isolates. Conclusion: Our results support that S. mutans clinical isolates have wide genotypic diversity and show variation in growth kinetics, acid production, acid tolerance and biofilm formation capacity and indicates the presence of diverse mechanism to initiate and establish the biofilm lifestyle which leads to tooth decay.

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

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.

Genetic linkage between altered tooth and eye development in lens-ablated Astyanax mexicanus

2018 ◽  
Vol 441 (2) ◽  
pp. 235-241 ◽  
Author(s):  
Atukorallaya Devi Sewvandini Atukorala ◽  
Tamara Anne Franz-Odendaal
Keyword(s):  
Genetic Linkage ◽  
Eye Development ◽  
Astyanax Mexicanus

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.

Lung cancer risk stratification using methylation profile in the oral epithelium

2018 ◽  
Vol 27 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Hiroaki Harada ◽  
Kazuaki Miyamaoto ◽  
Masami Kimura ◽  
Tetsuro Ishigami ◽  
Kiyomi Taniyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Cancer Risk ◽  
Risk Stratification ◽  
Lung Cancer Risk ◽  
Cancer Risk Assessment ◽  
Oral Epithelium ◽  
Specific Gene ◽  
Aberrant Methylation ◽  
Cancer Genes

Background Assuming that the entire airway is affected by the same inhaled carcinogen, similar molecular alterations may occur in the lung and oral cavity. Thus, we hypothesized that DNA methylation profiles in the oral epithelium may be a promising biomarker for lung cancer risk stratification. Methods A methylation-specific polymerase chain reaction was performed on oral epithelium from 16 patients with lung cancer and 32 controls without lung cancer. Genes showing aberrant methylation profiles in the oral epithelium were compared between patients and controls. Results The analysis revealed that HOXD11 and PCDHGB6 were methylated more frequently in patients than in controls ( p = 0.0055 and p = 0.0247, respectively). Combined analyses indicated that 8 of 16 (50%) patients and 3 of 32 (9.4%) controls showed DNA methylation in both genes ( p = 0.0016). Among the population limited to current and former smokers, 6 of 11 (54.5%) patients showed methylation in both genes, compared to 1 of 17 (5.9%) controls ( p = 0.0037). In a subgroup analysis limited to the population above 50-years old, 8 of 16 (50%) patients and 2 of 16 (12.5%) controls showed methylation in both genes ( p = 0.0221). Conclusions The results of this study indicate that specific gene methylation in the oral epithelium might be a promising biomarker for lung cancer risk assessment, especially among smokers. Risk stratification through the analysis of DNA methylation profiles in the oral epithelium may be a useful and less invasive first-step approach in an efficient two-step lung cancer screening strategy.

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