Genome-wide analysis of DNA methylation reveals selection signatures of the grass carp during domestication

With the rapid development of aquaculture, many fish species are domesticated and brought into cultivation. In the process of domestication, the domesticated fish undergone intense selection pressures and develop some adaptations and phenotypic traits, namely selection signatures, such as growth and metabolism, immunity, foraging and learning behaviors. However, how this selection signatures emerges is still not clear and the knowledge of molecular epigenetic mechanisms underlying selection signatures in fish is still in its infancy. Thus, we used a farmed fish, grass carp (Ctenopharyngodon idellus), as model species to detect these selection signatures and identify the candidate differentially methylated genes that are closely associated with these selection signatures at the level of whole genome, investigating the role of DNA methylation in the emergence of selection signatures during domestication. Our results showed that domesticated grass carp demonstrated four selection signatures, including growth and metabolism, immunity, foraging and learning behaviors, and 38 candidate genes were found associated with these traits. 16 genes are significant candidate genes which play major roles in the growth and metabolism, such as IGF-1 , GK , GYS1, etc. 11 genes are related to immunity, including . The GRM1, TAS1R1 and TAS1R3 genes are essential for the adaptation of domesticated grass carp to commercial feed in artificial rearing condition. The C-FOS, POMC and CBP genes may be responsible for the acquisition of novel feeding habits and contribute to faster growth indirectly by enhancing food intake. The findings here in will provide new insights to expand our understanding about the role of epigenetic modifications in shaping physiological phenotypes in this and other teleost models, which can contribute to efficient breeding of aquaculture stocks and restocking programmes.

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The role of DNA methylation in syndromic and non-syndromic congenital heart disease

Clinical Epigenetics ◽

10.1186/s13148-021-01077-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Jiali Cao ◽

Qichang Wu ◽

Yanru Huang ◽

Lingye Wang ◽

Zhiying Su ◽

...

Keyword(s):

Dna Methylation ◽

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart ◽

Chromosomal Abnormalities ◽

Cardiac Development ◽

Sample Type ◽

Differentially Methylated Genes ◽

Aberrant Dna Methylation

AbstractCongenital heart disease (CHD) is a common structural birth defect worldwide, and defects typically occur in the walls and valves of the heart or enlarged blood vessels. Chromosomal abnormalities and genetic mutations only account for a small portion of the pathogenic mechanisms of CHD, and the etiology of most cases remains unknown. The role of epigenetics in various diseases, including CHD, has attracted increased attention. The contributions of DNA methylation, one of the most important epigenetic modifications, to CHD have not been illuminated. Increasing evidence suggests that aberrant DNA methylation is related to CHD. Here, we briefly introduce DNA methylation and CHD and then review the DNA methylation profiles during cardiac development and in CHD, abnormalities in maternal genome-wide DNA methylation patterns are also described. Whole genome methylation profile and important differentially methylated genes identified in recent years are summarized and clustered according to the sample type and methodologies. Finally, we discuss the novel technology for and prospects of CHD-related DNA methylation.

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Regulation of Canonical Oncogenic Signaling Pathways in Cancer via DNA Methylation

Cancers ◽

10.3390/cancers12113199 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3199

Author(s):

Jennifer Lu ◽

Premila Wilfred ◽

Darren Korbie ◽

Matt Trau

Keyword(s):

Dna Methylation ◽

Signaling Pathways ◽

Biomarker Discovery ◽

Oncogenic Signaling ◽

Tissue Samples ◽

Epigenetic Biomarkers ◽

Differentially Methylated Genes ◽

Oncogenic Signaling Pathways ◽

Integration Analysis

Disruption of signaling pathways that plays a role in the normal development and cellular homeostasis may lead to the dysregulation of cellular signaling and bring about the onset of different diseases, including cancer. In addition to genetic aberrations, DNA methylation also acts as an epigenetic modifier to drive the onset and progression of cancer by mediating the reversible transcription of related genes. Although the role of DNA methylation as an alternative driver of carcinogenesis has been well-established, the global effects of DNA methylation on oncogenic signaling pathways and the presentation of cancer is only emerging. In this article, we introduced a differential methylation parsing pipeline (MethylMine) which mined for epigenetic biomarkers based on feature selection. This pipeline was used to mine for biomarkers, which presented a substantial difference in methylation between the tumor and the matching normal tissue samples. Combined with the Data Integration Analysis for Biomarker discovery (DIABLO) framework for machine learning and multi-omic analysis, we revisited the TCGA DNA methylation and RNA-Seq datasets for breast, colorectal, lung, and prostate cancer, and identified differentially methylated genes within the NRF2-KEAP1/PI3K oncogenic pathway, which regulates the expression of cytoprotective genes, that serve as potential therapeutic targets to treat different cancers.

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Methylation and Gene Expression Differences Between Reproductive Castes of Bumblebee Workers

10.1101/517698 ◽

2019 ◽

Cited By ~ 3

Author(s):

Hollie Marshall ◽

Zoë N. Lonsdale ◽

Eamonn B. Mallon

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Social Insects ◽

Social Insect ◽

Bombus Terrestris ◽

Epigenetic Mechanisms ◽

Biological Processes ◽

Caste Determination ◽

Differentially Methylated Genes

AbstractPhenotypic plasticity is the production of multiple phenotypes from a single genome and is notably observed in social insects. Multiple epigenetic mechanisms have been associated with social insect plasticity, with DNA methylation being explored to the greatest extent. DNA methylation is thought to play a role in caste determination in Apis mellifera, and other social insects, but there is limited knowledge on it’s role in other bee species. In this study we analysed whole genome bisulfite sequencing and RNA-seq data sets from head tissue of reproductive and sterile castes of the eusocial bumblebee Bombus terrestris. We found genome-wide methylation in B. terrestris is similar to other social insects and does not differ between reproductive castes. We did, however, find differentially methylated genes between castes, which are enriched for multiple biological processes including reproduction. However we found no relationship between differential methylation and differential gene expression or differential exon usage between castes. Our results also indicate high inter-colony variation in methylation. These findings suggest methylation is associated with caste differences but may serve an alternate function, other than direct caste determination in this species. This study provides the first insights into the nature of a bumblebee caste specific methylome as well as it’s interaction with gene expression and caste specific alternative splicing, providing greater understanding of the role of methylation in phenotypic plasticity within social bee species. Future experimental work is needed to determine the function of methylation and other epigenetic mechanisms in social insects.Impact SummarySocial insects, such as ants, termites, bees and wasps, can produce individuals with extreme physical and behavioural differences within the same colony known as castes (e.g. workers/soldiers/queens). These individuals have similar genomes and many studies have associated epigenetic mechanisms with the differences observed. Epigenetic modifications are changes that affect how genes are expressed without changing the underlying DNA code. Here we investigated differences in DNA methylation (a well researched modified base) between different reproductive castes of the bumblebee, Bombus terrestris, an economically and environmentally important pollinator species. We found B. terrestris has a similar methylation profile to other social insect species in terms of the distribution of methylation throughout the genome and the relationship between methylation and gene expression. Genes that have differences in methylation between reproductive castes are involved in multiple biological processes, including reproduction, suggesting methylation may hold multiple functions in this species. These differentially methylated genes are also different to differentially methylated genes identified between honeybee reproductive castes, again suggesting methylation may have a variable function. These findings provide greater understanding of the role of methylation in caste determination in social insect species.

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Network Analysis of the Potential Role of DNA Methylation in the Relationship between Plasma Carotenoids and Lipid Profile

Nutrients ◽

10.3390/nu11061265 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1265 ◽

Cited By ~ 3

Author(s):

Bénédicte L. Tremblay ◽

Frédéric Guénard ◽

Benoît Lamarche ◽

Louis Pérusse ◽

Marie-Claude Vohl

Keyword(s):

Dna Methylation ◽

Network Analysis ◽

Lipid Profile ◽

Gene Clusters ◽

Phenotypic Traits ◽

Total Carotenoid ◽

Hub Genes ◽

The Impact ◽

The Relationship

Variability in plasma carotenoids may be attributable to several factors including genetic variants and lipid profile. Until now, the impact of DNA methylation on this variability has not been widely studied. Weighted gene correlation network analysis (WGCNA) is a systems biology method used for finding gene clusters (modules) with highly correlated methylation levels and for relating them to phenotypic traits. The objective of the present study was to examine the role of DNA methylation in the relationship between plasma total carotenoid concentrations and lipid profile using WGCNA in 48 healthy subjects. Genome-wide DNA methylation levels of 20,687 out of 472,245 CpG sites in blood leukocytes were associated with total carotenoid concentrations. Using WGCNA, nine co-methylation modules were identified. A total of 2734 hub genes (17 unique top hub genes) were potentially related to lipid profile. This study provides evidence for the potential implications of gene co-methylation in the relationship between plasma carotenoids and lipid profile. Further studies and validation of the hub genes are needed.

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Challenges in nutrition-related DNA methylation studies

BioMolecular Concepts ◽

10.1515/bmc-2011-0052 ◽

2012 ◽

Vol 3 (2) ◽

pp. 151-160 ◽

Cited By ~ 4

Author(s):

Mihai D. Niculescu

Keyword(s):

Dna Methylation ◽

Rapid Development ◽

Bioinformatic Analysis ◽

Detection Methods ◽

Rapid Progress ◽

Treatment Groups ◽

Quality Detection ◽

Genome Wide ◽

Final Interpretation

AbstractThe rapid progress in nutritional epigenetics allowed for a much better understanding of the mechanisms involved in gene-nutrient interactions and the roles that nutrition has in transgenerational inheritance of acquired epigenetic traits. Studies indicated that a considerable number of nutrients or diet types are capable of inducing epimutations. In parallel, the rapid development of genome-wide DNA methylation detection methods allowed for a broader image on how nutrition impacts the epigenetic status in human and animal models. But this increased complexity in the epigenetic field and also brought important challenges that need resolution, or it suggests that some of the initial epigenetic paradigms have to be revisited or reconsidered. The aim of this review is to discuss the inherent challenges that need to be resolved, from both practical and theoretical aspects, stemming from the rapid progress in the field of nutritional epigenetics, with a focus on DNA methylation. Because such challenges are present at every stage of study development, the review systematically discusses the most common issues relevant to DNA methylation in a nutritional context. Various types of challenges and potential bias generators are discussed within study design, sample quality, detection methods, data processing, and statistical and bioinformatic analysis. Additional aspects to be considered include epigenetic heterogeneity of treatment groups, the role of genomic variability in introducing measurement bias and errors in interpretation of changes, and issues related to the final interpretation of results and in assigning functional significance. It is also posited that all these issues will be largely resolved within the next decade.

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DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Non-syndromic Cleft Lip and Palate

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.656865 ◽

2021 ◽

Vol 9 ◽

Author(s):

Juan I. Young ◽

Susan Slifer ◽

Jacqueline T. Hecht ◽

Susan H. Blanton

Keyword(s):

Dna Methylation ◽

Candidate Genes ◽

Dna Sequences ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Differential Methylation ◽

Potential Contribution ◽

Hippo Signaling ◽

Mz Twins

Non-syndromic cleft lip with or without cleft palate (NSCLP) is the most common craniofacial birth defect. The etiology of NSCLP is complex with multiple genes and environmental factors playing causal roles. Although studies have identified numerous genetic markers associated with NSCLP, the role of epigenetic variation remains relatively unexplored. Because of their identical DNA sequences, monozygotic (MZ) twins discordant for NSCLP are an ideal model for examining the potential contribution of DNA methylation to non-syndromic orofacial clefting. In this study, we compared the patterns of whole genome DNA methylation in six MZ twin pairs discordant for NSCLP. Differentially methylated positions (DMPs) and regions (DMRs) were identified in NSCLP candidate genes, including differential methylation in MAFB and ZEB2 in two independent MZ twin pairs. In addition to DNA methylation differences in NSCLP candidate genes, we found common differential methylation in genes belonging to the Hippo signaling pathway, implicating this mechanosensory pathway in the etiology of NSCLP. The results of this novel approach using MZ twins discordant for NSCLP suggests that differential methylation is one mechanism contributing to NSCLP, meriting future studies on the role of DNA methylation in familial and sporadic NSCLP.

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DNA methylation in satellite repeats disorders

Essays in Biochemistry ◽

10.1042/ebc20190028 ◽

2019 ◽

Vol 63 (6) ◽

pp. 757-771 ◽

Cited By ~ 4

Author(s):

Claire Francastel ◽

Frédérique Magdinier

Keyword(s):

Dna Methylation ◽

Human Genome ◽

Repetitive Dna ◽

Dna Sequences ◽

Satellite Repeats ◽

Tremendous Progress ◽

Genes Encoding ◽

Dna Elements ◽

Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

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