scholarly journals The Bright and Dark Side of DNA Methylation: A Matter of Balance

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1243 ◽  
Author(s):  
Marta Borchiellini ◽  
Simone Ummarino ◽  
Annalisa Di Ruscio
Keyword(s):  
Dna Methylation ◽  
Developmental Stages ◽  
Germ Line ◽  
Dark Side ◽  
Epigenetic Mark ◽  
Cellular Processes ◽  
Biological Responses ◽  
Molecular Events ◽  
Genome Wide ◽  
Health Related

DNA methylation controls several cellular processes, from early development to old age, including biological responses to endogenous or exogenous stimuli contributing to disease transition. As a result, minimal DNA methylation changes during developmental stages drive severe phenotypes, as observed in germ-line imprinting disorders, while genome-wide alterations occurring in somatic cells are linked to cancer onset and progression. By summarizing the molecular events governing DNA methylation, we focus on the methods that have facilitated mapping and understanding of this epigenetic mark in healthy conditions and diseases. Overall, we review the bright (health-related) and dark (disease-related) side of DNA methylation changes, outlining how bulk and single-cell genomic analyses are moving toward the identification of new molecular targets and driving the development of more specific and less toxic demethylating agents.

scholarly journals A model for the aberrant DNA methylomes in aging cells and cancer cells

2019 ◽  
Vol 47 (4) ◽  
pp. 997-1003 ◽  
Author(s):  
Huiming Zhang ◽  
Kang Zhang ◽  
Jian-Kang Zhu
Keyword(s):  
Dna Methylation ◽  
Cancer Cells ◽  
Developmental Stages ◽  
Methylation Pattern ◽  
Epigenetic Mark ◽  
Dna Hypomethylation ◽  
Genome Wide ◽  
Abnormal Cells ◽  
Genomic Regions ◽  
Methylation Patterns

Abstract DNA methylation at the fifth position of cytosine is a major epigenetic mark conserved in plants and mammals. Genome-wide DNA methylation patterns are dynamically controlled by integrated activities of establishment, maintenance, and removal. In both plants and mammals, a pattern of global DNA hypomethylation coupled with increased methylation levels at some specific genomic regions arises at specific developmental stages and in certain abnormal cells, such as mammalian aging cells and cancer cells as well as some plant epigenetic mutants. Here we provide an overview of this distinct DNA methylation pattern in mammals and plants, and propose that a methylstat, which is a cis-element responsive to both DNA methylation and active demethylation activities and controlling the transcriptional activity of a key DNA methylation regulator, can help to explain the enigmatic DNA methylation patterns in aging cells and cancer cells.

scholarly journals Efficient and accurate determination of genome-wide DNA methylation patterns in Arabidopsis thaliana with enzymatic methyl sequencing

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Suhua Feng ◽  
Zhenhui Zhong ◽  
Ming Wang ◽  
Steven E. Jacobsen
Keyword(s):  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Accurate Determination ◽  
Gc Content ◽  
Epigenetic Mark ◽  
Whole Genome ◽  
Whole Genome Bisulfite Sequencing ◽  
Genome Wide ◽  
A Genome ◽  
Genome Bisulfite Sequencing

Abstract Background 5′ methylation of cytosines in DNA molecules is an important epigenetic mark in eukaryotes. Bisulfite sequencing is the gold standard of DNA methylation detection, and whole-genome bisulfite sequencing (WGBS) has been widely used to detect methylation at single-nucleotide resolution on a genome-wide scale. However, sodium bisulfite is known to severely degrade DNA, which, in combination with biases introduced during PCR amplification, leads to unbalanced base representation in the final sequencing libraries. Enzymatic conversion of unmethylated cytosines to uracils can achieve the same end product for sequencing as does bisulfite treatment and does not affect the integrity of the DNA; enzymatic methylation sequencing may, thus, provide advantages over bisulfite sequencing. Results Using an enzymatic methyl-seq (EM-seq) technique to selectively deaminate unmethylated cytosines to uracils, we generated and sequenced libraries based on different amounts of Arabidopsis input DNA and different numbers of PCR cycles, and compared these data to results from traditional whole-genome bisulfite sequencing. We found that EM-seq libraries were more consistent between replicates and had higher mapping and lower duplication rates, lower background noise, higher average coverage, and higher coverage of total cytosines. Differential methylation region (DMR) analysis showed that WGBS tended to over-estimate methylation levels especially in CHG and CHH contexts, whereas EM-seq detected higher CG methylation levels in certain highly methylated areas. These phenomena can be mostly explained by a correlation of WGBS methylation estimation with GC content and methylated cytosine density. We used EM-seq to compare methylation between leaves and flowers, and found that CHG methylation level is greatly elevated in flowers, especially in pericentromeric regions. Conclusion We suggest that EM-seq is a more accurate and reliable approach than WGBS to detect methylation. Compared to WGBS, the results of EM-seq are less affected by differences in library preparation conditions or by the skewed base composition in the converted DNA. It may therefore be more desirable to use EM-seq in methylation studies.

scholarly journals Seasonal Stability and Dynamics of DNA Methylation in Plants in a Natural Environment

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 544 ◽  
Author(s):  
Ito ◽  
Nishio ◽  
Tarutani ◽  
Emura ◽  
Honjo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Repetitive Sequences ◽  
Epigenetic Mark ◽  
Stable Gene ◽  
Natural Environments ◽  
Arabidopsis Halleri ◽  
Genome Wide ◽  
Single Clone ◽  
Intergenic Regions ◽  
Stable Gene Expression

: DNA methylation has been considered a stable epigenetic mark but may respond to fluctuating environments. However, it is unclear how they behave in natural environments. Here, we analyzed seasonal patterns of genome-wide DNA methylation in a single clone from a natural population of the perennial Arabidopsis halleri. The genome-wide pattern of DNA methylation was primarily stable, and most of the repetitive regions were methylated across the year. Although the proportion was small, we detected seasonally methylated cytosines (SeMCs) in the genome. SeMCs in the CHH context were detected predominantly at repetitive sequences in intergenic regions. In contrast, gene-body CG methylation (gbM) itself was generally stable across seasons, but the levels of gbM were positively associated with seasonal stability of RNA expression of the genes. These results suggest the existence of two distinct aspects of DNA methylation in natural environments: sources of epigenetic variation and epigenetic marks for stable gene expression.

scholarly journals Community-wide epigenetics provides novel perspectives on the ecology and evolution of marine microbiome

2021 ◽  
Author(s):  
Hoon Je Seong ◽  
Simon Roux ◽  
Chung Yeon Hwang ◽  
Woo Jun Sul
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Distribution Patterns ◽  
Cellular Processes ◽  
Genome Wide ◽  
Methylation Mark ◽  
Domains Of Life ◽  
Epigenetic Analysis ◽  
Cycle Regulation

DNA methylation in prokaryotes is involved in many different cellular processes including cell cycle regulation and defense against viruses. To date, most prokaryotic methylation systems have been studied in culturable microorganisms, resulting in a limited understanding of DNA methylation from a microbial ecology perspective. Here, we analyze the distribution patterns of several microbial epigenetics marks in the ocean microbiome through genome-centric metagenomics across all domains of life. We show that overall, DNA methylation can readily be detected across dominant oceanic bacterial, archaeal, and viral populations, and microbial epigenetic changes correlate with population differentiation. Furthermore, our genome-wide epigenetic analysis of Pelagibacter suggests that GANTC, a DNA methyltransferase target motif, is related to the cell cycle and is affected by environmental conditions. Yet, the presence of this motif also partitions the phylogeny of the Pelagibacter phages, possibly hinting at a competitive co-evolutionary history and multiple effects of a single methylation mark.

scholarly journals Global DNA methylation: role, status and genome-wide approaches to study epigenetic mark in cloned embryos

2020 ◽  
pp. 41-59
Author(s):  
Shivani Malpotra ◽  
Ahmad Hussain
Keyword(s):  
Dna Methylation ◽  
Developmental Stages ◽  
Gene Expression Pattern ◽  
Methylation Profile ◽  
Global Dna Methylation ◽  
Epigenetic Mark ◽  
Dna Methylation Profile ◽  
Low Efficiency

Somatic cell nuclear transfer (SCNT) technique has been proving its worth for more than two decades now as over 20 different species have been successfully cloned. SCNT protocol for cloning is well established but efficiency in terms of live birth rate is still low. Epigenetic abnormality following nuclear reprogramming is considered as the main culprit behind its low efficiency. DNA methylation is one of the most important epigenetic modifications that directly or indirectly regulate gene expression pattern, development and genome stability. Embryos produced through SCNT are found to express abnormal DNA methylation profile in comparison with in vivo or in vitro produced embryos. In order to improve DNA methylation profile in cloned embryos, a complete database of whole genome is required to find out specific faulty targets. Many techniques including low throughput and high throughput approach has been used to profile DNA methylation pattern in bovine embryos throughout the developmental stages. In the present review, we have compiled the overall status of global DNA methylation, the effect of aberrant DNA methylation on development and evolution in methodologies used for profiling global DNA methylome in cloned embryos.

scholarly journals Title: Hypermethylation of miRNA Genes During Nodule Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Sarbottam Piya ◽  
Valeria S. Lopes-Caitar ◽  
Won‐Seok Kim ◽  
Vince Pantalone ◽  
Hari B. Krishnan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Developmental Stages ◽  
Nodule Development ◽  
Nodule Formation ◽  
Primary Transcript ◽  
Cellular Processes ◽  
Mirna Genes ◽  
Root Tissues ◽  
Methylation Patterns

DNA methylation has recently emerged as a powerful regulatory mechanism controlling the expression of key regulators of various developmental processes, including nodulation. However, the functional role of DNA methylation in regulating the expression of microRNA (miRNA) genes during the formation and development of nitrogen-fixing nodules remains largely unknown. In this study, we profiled DNA methylation patterns of miRNA genes during nodule formation, development, and early senescence stages in soybean (Glycine max) through the analysis of methylC—seq data. Absolute DNA methylation levels in the CG, CHH, and CHH sequence contexts over the promoter and primary transcript regions of miRNA genes were significantly higher in the nodules compared with the corresponding root tissues at these three distinct nodule developmental stages. We identified a total of 82 differentially methylated miRNAs in the nodules compared with roots. Differential DNA methylation of these 82 miRNAs was detected only in the promoter (69), primary transcript region (3), and both in the promoter and primary transcript regions (10). The large majority of these differentially methylated miRNAs were hypermethylated in nodules compared with the corresponding root tissues and were found mainly in the CHH context and showed stage-specific methylation patterns. Differentially methylated regions in the promoters of 25 miRNAs overlapped with transposable elements, a finding that may explain the vulnerability of miRNAs to DNA methylation changes during nodule development. Gene expression analysis of a set of promoter-differentially methylated miRNAs pointed to a negative association between DNA methylation and miRNA expression. Gene Ontology and pathways analyses indicate that changes in DNA methylation of miRNA genes are reprogrammed and contribute to nodule development through indirect regulation of genes involved in cellular processes and pathways with well-established roles in nodulation.

scholarly journals Global reinforcement of DNA methylation through enhancement of RNA-directed DNA methylation ensures sexual reproduction in rice

2020 ◽  
Author(s):  
Lili Wang ◽  
Longjun Zeng ◽  
Kezhi Zheng ◽  
Tianxin Zhu ◽  
Yumeng Yin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Sexual Reproduction ◽  
De Novo ◽  
Rice Genome ◽  
Biological Significance ◽  
Reproductive Organs ◽  
Epigenetic Mark ◽  
Small Interfering Rnas ◽  
Genome Wide ◽  
Global Increase

AbstractDNA methylation is an important epigenetic mark that regulates the expression of genes and transposons. RNA-directed DNA methylation (RdDM) is the main molecular pathway responsible for de novo DNA methylation in plants. In Arabidopsis, however, mutations in RdDM genes cause no visible developmental defects, which raising the question of the biological significance of RdDM in plant development. Here, we isolated and cloned Five Elements Mountain 1 (FEM1), which encodes an RNA-dependent RNA polymerase. Mutation in FEM1 substantially decreased genome-wide CHH methylation levels and abolished the accumulation of 24-nt small interfering RNAs. Moreover, male and female reproductive development was disturbed, which led to the sterility of fem1 mutants. In wild-type (WT) plants but not in fem1 mutants, genome-wide CHH DNA methylation levels were greater in panicles, stamens, and pistils than in seedlings. The global increase of methylation in reproductive organs of the WT was attributed to enhancement of RdDM activity including FEM1 activity. More than half of all encoding genes in the rice genome overlapped with hypermethylated regions in the sexual organs of the WT, and many of them appear to be directly regulated by an increase in DNA methylation.Our results demonstrate that a global increase of DNA methylation through enhancement of RdDM activity in reproductive organs ensures sexual reproduction of rice.

scholarly journals Common alleles of CMT2 and NRPE1 are major determinants of de novo DNA methylation variation in Arabidopsis thaliana

2019 ◽  
Author(s):  
Eriko Sasaki ◽  
Taiji Kawakatsu ◽  
Joseph Ecker ◽  
Magnus Nordborg
Keyword(s):  
Dna Methylation ◽  
Large Scale ◽  
Cytosine Methylation ◽  
De Novo ◽  
Association Studies ◽  
Published Data ◽  
Epigenetic Mark ◽  
Stabilizing Selection ◽  
Genome Wide Association Studies ◽  
Genome Wide

AbstractDNA cytosine methylation is an epigenetic mark associated with silencing of transposable elements (TEs) and heterochromatin formation. In plants, it occurs in three sequence contexts: CG, CHG, and CHH (where H is A, T, or C). The latter does not allow direct inheritance of methylation during DNA replication due to lack of symmetry, and methylation must therefore be re-established every cell generation. Genome-wide association studies (GWAS) have previously shown that CMT2 and NRPE1 are major determinants of genome-wide patterns of TE CHH-methylation. Here we instead focus on CHH-methylation of individual TEs and TE-families, allowing us to identify the pathways involved in CHH-methylation simply from natural variation and confirm the associations by comparing them with mutant phenotypes. Methylation at TEs targeted by the RNA-directed DNA methylation (RdDM) pathway is unaffected by CMT2 variation, but is strongly affected by variation at NRPE1, which is largely responsible for the longitudinal cline in this phenotype. In contrast, CMT2-targeted TEs are affected by both loci, which jointly explain 7.3% of the phenotypic variation (13.2% of total genetic effects). There is no longitudinal pattern for this phenotype, however, because the geographic patterns appear to compensate for each other in a pattern suggestive of stabilizing selection.Author SummaryDNA methylation is a major component of transposon silencing, and essential for genomic integrity. Recent studies revealed large-scale geographic variation as well as the existence of major trans-acting polymorphisms that partly explained this variation. In this study, we re-analyze previously published data (The 1001 Epigenomes), focusing on de novo DNA methylation patterns of individual TEs and TE families rather than on genome-wide averages (as was done in previous studies). GWAS of the patterns reveals the underlying regulatory networks, and allowed us to comprehensively characterize trans-regulation of de novo DNA methylation and its role in the striking geographic pattern for this phenotype.

scholarly journals DNA Methylation Alterations in Blood Cells of Toddlers with Down Syndrome

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1115
Author(s):  
Oxana Yu. Naumova ◽  
Rebecca Lipschutz ◽  
Sergey Yu. Rychkov ◽  
Olga V. Zhukova ◽  
Elena L. Grigorenko
Keyword(s):  
Dna Methylation ◽  
Down Syndrome ◽  
Blood Cells ◽  
Trisomy 21 ◽  
Developmental Stages ◽  
Published Data ◽  
Age Group ◽  
Genome Wide ◽  
Prior Literature ◽  
Methylation Patterns

Recent research has provided evidence on genome-wide alterations in DNA methylation patterns due to trisomy 21, which have been detected in various tissues of individuals with Down syndrome (DS) across different developmental stages. Here, we report new data on the systematic genome-wide DNA methylation perturbations in blood cells of individuals with DS from a previously understudied age group—young children. We show that the study findings are highly consistent with those from the prior literature. In addition, utilizing relevant published data from two other developmental stages, neonatal and adult, we track a quasi-longitudinal trend in the DS-associated DNA methylation patterns as a systematic epigenomic destabilization with age.

scholarly journals Recent progress towards understanding the role of DNA methylation in human placental development

Reproduction ◽  
2016 ◽  
Vol 152 (1) ◽  
pp. R23-R30 ◽  
Author(s):  
Tina Bianco-Miotto ◽  
Benjamin T Mayne ◽  
Sam Buckberry ◽  
James Breen ◽  
Carlos M Rodriguez Lopez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Pregnancy Complications ◽  
Large Scale ◽  
Developmental Stages ◽  
Epigenetic Modifications ◽  
Placental Development ◽  
Functional Changes ◽  
Genome Wide

Epigenetic modifications, and particularly DNA methylation, have been studied in many tissues, both healthy and diseased, and across numerous developmental stages. The placenta is the only organ that has a transient life of 9 months and undergoes rapid growth and dynamic structural and functional changes across gestation. Additionally, the placenta is unique because although developing within the mother, its genome is identical to that of the foetus. Given these distinctive characteristics, it is not surprising that the epigenetic landscape affecting placental gene expression may be different to that in other healthy tissues. However, the role of epigenetic modifications, and particularly DNA methylation, in placental development remains largely unknown. Of particular interest is the fact that the placenta is the most hypomethylated human tissue and is characterized by the presence of large partially methylated domains (PMDs) containing silenced genes. Moreover, how and why the placenta is hypomethylated and what role DNA methylation plays in regulating placental gene expression across gestation are poorly understood. We review genome-wide DNA methylation studies in the human placenta and highlight that the different cell types that make up the placenta have very different DNA methylation profiles. Summarizing studies on DNA methylation in the placenta and its relationship with pregnancy complications are difficult due to the limited number of studies available for comparison. To understand the key steps in placental development and hence what may be perturbed in pregnancy complications requires large-scale genome-wide DNA methylation studies coupled with transcriptome analyses.

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