DNA methylation-linked chromatin accessibility affects genomic architecture in Arabidopsis

DNA methylation is a major epigenetic modification found across species and has a profound impact on many biological processes. However, its influence on chromatin accessibility and higher-order genome organization remains unclear, particularly in plants. Here, we present genome-wide chromatin accessibility profiles of 18 Arabidopsis mutants that are deficient in CG, CHG, or CHH DNA methylation. We find that DNA methylation in all three sequence contexts impacts chromatin accessibility in heterochromatin. Many chromatin regions maintain inaccessibility when DNA methylation is lost in only one or two sequence contexts, and signatures of accessibility are particularly affected when DNA methylation is reduced in all contexts, suggesting an interplay between different types of DNA methylation. In addition, we found that increased chromatin accessibility was not always accompanied by increased transcription, suggesting that DNA methylation can directly impact chromatin structure by other mechanisms. We also observed that an increase in chromatin accessibility was accompanied by enhanced long-range chromatin interactions. Together, these results provide a valuable resource for chromatin architecture and DNA methylation analyses and uncover a pivotal role for methylation in the maintenance of heterochromatin inaccessibility.

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Genome-wide DNA methylation profiles of porcine ovaries in estrus and proestrus

Physiological Genomics ◽

10.1152/physiolgenomics.00052.2017 ◽

2018 ◽

Vol 50 (9) ◽

pp. 714-723 ◽

Cited By ~ 1

Author(s):

Xiaolong Zhou ◽

Songbai Yang ◽

Feifei Yan ◽

Ke He ◽

Ayong Zhao

Keyword(s):

Dna Methylation ◽

Epigenetic Modification ◽

Cpg Islands ◽

Biological Processes ◽

Hormone Regulation ◽

Methylated Dna ◽

Coding Regions ◽

Genome Wide ◽

Differentially Methylated Genes ◽

Flanking Regions

DNA methylation is an important epigenetic modification involved in the estrous cycle and the regulation of reproduction. Here, we investigated the genome-wide profiles of DNA methylation in porcine ovaries in proestrus and estrus using methylated DNA immunoprecipitation sequencing. The results showed that DNA methylation was enriched in intergenic and intron regions. The methylation levels of coding regions were higher than those of the 5′- and 3′-flanking regions of genes. There were 4,813 differentially methylated regions (DMRs) of CpG islands in the estrus vs. proestrus ovarian genomes. Additionally, 3,651 differentially methylated genes (DMGs) were identified in pigs in estrus and proestrus. The DMGs were significantly enriched in biological processes and pathways related to reproduction and hormone regulation. We identified 90 DMGs associated with regulating reproduction in pigs. Our findings can serve as resources for DNA methylome research focused on porcine ovaries and further our understanding of epigenetically regulated reproduction in mammals.

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A pooling-based approach to mapping genetic variants associated with DNA methylation

10.1101/013649 ◽

2015 ◽

Cited By ~ 1

Author(s):

Irene Miriam Kaplow ◽

Julia L MacIsaac ◽

Sarah M Mah ◽

Lisa M McEwen ◽

Michael S Kobor ◽

...

Keyword(s):

Dna Methylation ◽

Genetic Variants ◽

Statistical Power ◽

Epigenetic Modification ◽

Chromatin Accessibility ◽

Ctcf Binding ◽

Sequencing Data ◽

Individual Level ◽

Novel Approach ◽

Genome Wide

DNA methylation is an epigenetic modification that plays a key role in gene regulation. Previous studies have investigated its genetic basis by mapping genetic variants that are associated with DNA methylation at specific sites, but these have been limited to microarrays that cover less than 2% of the genome and cannot account for allele-specific methylation (ASM). Other studies have performed whole-genome bisulfite sequencing on a few individuals, but these lack statistical power to identify variants associated with DNA methylation. We present a novel approach in which bisulfite-treated DNA from many individuals is sequenced together in a single pool, resulting in a truly genome-wide map of DNA methylation. Compared to methods that do not account for ASM, our approach increases statistical power to detect associations while sharply reducing cost, effort, and experimental variability. As a proof of concept, we generated deep sequencing data from a pool of 60 human cell lines; we evaluated almost twice as many CpGs as the largest microarray studies and identified over 2,000 genetic variants associated with DNA methylation. We found that these variants are highly enriched for associations with chromatin accessibility and CTCF binding but are less likely to be associated with traits indirectly linked to DNA, such as gene expression and disease phenotypes. In summary, our approach allows genome-wide mapping of genetic variants associated with DNA methylation in any tissue of any species, without the need for individual-level genotype or methylation data.

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Genome-Wide DNA Methylation Profiling in the Lotus (Nelumbo nucifera) Flower Showing its Contribution to the Stamen Petaloid

Plants ◽

10.3390/plants8050135 ◽

2019 ◽

Vol 8 (5) ◽

pp. 135 ◽

Cited By ~ 5

Author(s):

Zhongyuan Lin ◽

Meihui Liu ◽

Rebecca Njeri Damaris ◽

Tonny Maraga Nyong’a ◽

Dingding Cao ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Bisulfite Sequencing ◽

Epigenetic Modification ◽

Nelumbo Nucifera ◽

Flower Formation ◽

Relationship Analysis ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

DNA methylation is a vital epigenetic modification. Methylation has a significant effect on the gene expression influencing the regulation of different physiological processes. Current studies on DNA methylation have been conducted on model plants. Lotus (Nelumbo nucifera) is a basic eudicot exhibiting variations during development, especially in flower formation. DNA methylation profiling was conducted on different flower tissues of lotuses through whole genome bisulfite sequencing (WGBS) to investigate the effects of DNA methylation on its stamen petaloid. A map of methylated cytosines at the single base pair resolution for the lotus was constructed. When the stamen was compared with the stamen petaloid, the DNA methylation exhibited a global decrease. Genome-wide relationship analysis between DNA methylation and gene expression identified 31 different methylation region (DMR)-associated genes, which might play crucial roles in floral organ formation, especially in the stamen petaloid. One out of 31 DMR-associated genes, NNU_05638 was homolog with Plant U-box 33 (PUB33). The DNA methylation status of NNU_05638 promoter was distinct in three floral organs, which was confirmed by traditional bisulfite sequencing. These results provide further insights about the regulation of stamen petaloids at the epigenetic level in lotus.

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Genome-Wide Differential DNA Methylation and miRNA Expression Profiling Reveals Epigenetic Regulatory Mechanisms Underlying Nitrogen-Limitation-Triggered Adaptation and Use Efficiency Enhancement in Allotetraploid Rapeseed

International Journal of Molecular Sciences ◽

10.3390/ijms21228453 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8453

Author(s):

Ying-peng Hua ◽

Ting Zhou ◽

Jin-yong Huang ◽

Cai-peng Yue ◽

Hai-xing Song ◽

...

Keyword(s):

Dna Methylation ◽

Epigenetic Modification ◽

Lateral Roots ◽

Regulatory Mechanisms ◽

Crop Species ◽

N Limitation ◽

Genome Wide ◽

Differentially Methylated Genes ◽

N Metabolism ◽

Use Efficiency

Improving crop nitrogen (N) limitation adaptation (NLA) is a core approach to enhance N use efficiency (NUE) and reduce N fertilizer application. Rapeseed has a high demand for N nutrients for optimal plant growth and seed production, but it exhibits low NUE. Epigenetic modification, such as DNA methylation and modification from small RNAs, is key to plant adaptive responses to various stresses. However, epigenetic regulatory mechanisms underlying NLA and NUE remain elusive in allotetraploid B. napus. In this study, we identified overaccumulated carbohydrate, and improved primary and lateral roots in rapeseed plants under N limitation, which resulted in decreased plant nitrate concentrations, enhanced root-to-shoot N translocation, and increased NUE. Transcriptomics and RT-qPCR assays revealed that N limitation induced the expression of NRT1.1, NRT1.5, NRT1.7, NRT2.1/NAR2.1, and Gln1;1, and repressed the transcriptional levels of CLCa, NRT1.8, and NIA1. High-resolution whole genome bisulfite sequencing characterized 5094 differentially methylated genes involving ubiquitin-mediated proteolysis, N recycling, and phytohormone metabolism under N limitation. Hypermethylation/hypomethylation in promoter regions or gene bodies of some key N-metabolism genes might be involved in their transcriptional regulation by N limitation. Genome-wide miRNA sequencing identified 224 N limitation-responsive differentially expressed miRNAs regulating leaf development, amino acid metabolism, and plant hormone signal transduction. Furthermore, degradome sequencing and RT-qPCR assays revealed the miR827-NLA pathway regulating limited N-induced leaf senescence as well as the miR171-SCL6 and miR160-ARF17 pathways regulating root growth under N deficiency. Our study provides a comprehensive insight into the epigenetic regulatory mechanisms underlying rapeseed NLA, and it will be helpful for genetic engineering of NUE in crop species through epigenetic modification of some N metabolism-associated genes.

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Identification and characterization of the cytosine-5 DNA methyltransferase gene family in Salvia miltiorrhiza

PeerJ ◽

10.7717/peerj.4461 ◽

2018 ◽

Vol 6 ◽

pp. e4461 ◽

Cited By ~ 3

Author(s):

Jiang Li ◽

Caili Li ◽

Shanfa Lu

Keyword(s):

Dna Methylation ◽

Salicylic Acid ◽

Gene Family ◽

Sequence Alignment ◽

Dna Methyltransferase ◽

Epigenetic Modification ◽

Salvia Miltiorrhiza ◽

Dna Methyltransferases ◽

Genome Wide ◽

Wide Range

Cytosine DNA methylation is highly conserved epigenetic modification involved in a wide range of biological processes in eukaryotes. It was established and maintained by cytosine-5 DNA methyltransferases (C5-MTases) in plants. Through genome-wide identification, eight putative SmC5-MTase genes were identified from the genome of Salvia miltiorrhiza, a well-known traditional Chinese medicine material and an emerging model medicinal plant. Based on conserved domains and phylogenetic analysis, eight SmC5-MTase genes were divided into four subfamilies, including MET, CMT, DRM and DNMT2. Genome-wide comparative analysis of the C5-MTase gene family in S. miltiorrhiza and Arabidopsis thaliana, including gene structure, sequence features, sequence alignment and conserved motifs, was carried out. The results showed conservation and divergence of the members of each subfamily in plants. The length of SmC5-MTase open reading frames ranges widely from 1,152 (SmDNMT2) to 5,034 bp (SmMET1). The intron number of SmC5-MTases varies between 7 (SmDRM1) and 20 (SmCMT1 and SmCMT2b). These features were similar to their counterparts from Arabidopsis. Sequence alignment and conserved motif analysis showed the existence of highly conserved and subfamily-specific motifs in the C5-MTases analyzed. Differential transcript abundance was detected for SmC5-MTases, implying genome-wide variance of DNA methylation in different organs and tissues. Transcriptome-wide analysis showed that the transcript levels of all SmC5-MTase genes was slightly changed under yeast extract and methyl jasmonate treatments. Six SmC5-MTases, including SmMET1, SmCMT1, SmCMT2a, SmCMT2b, SmCMT3 and SmDRM1, were salicylic acid-responsive, suggesting the involvement of SmC5-MTases in salicylic acid-dependent immunity. These results provide useful information for demonstrating the role of DNA methylation in bioactive compound biosynthesis and Dao-di herb formation in medicinal plants.

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Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference

10.1101/823807 ◽

2019 ◽

Cited By ~ 1

Author(s):

Paul J. Hop ◽

René Luijk ◽

Lucia Daxinger ◽

Maarten van Iterson ◽

Koen F. Dekkers ◽

...

Keyword(s):

Dna Methylation ◽

Large Scale ◽

Population Genomics ◽

Epigenetic Modification ◽

Binding Activity ◽

Dna Binding Activity ◽

Genome Wide ◽

Scale Population ◽

Genes Encoding ◽

Methylation Patterns

SUMMARYDNA methylation is a key epigenetic modification in human development and disease, yet there is limited understanding of its highly coordinated regulation. Here, we identified 818 genes that influence DNA methylation patterns in blood using large-scale population genomics data. By employing genetic instruments as causal anchors, we identified directed associations between gene expression and distant DNA methylation levels, whilst ensuring specificity of the associations by correcting for linkage disequilibrium and pleiotropy among neighboring genes. We found that DNA methylation patterns are commonly shaped by transcription factors that consistently increase or decrease DNA methylation levels. However, we also observed genes encoding proteins without DNA binding activity with widespread effects on DNA methylation (e.g. NFKBIE, CDCA7(L) and NLRC5) and we suggest plausible mechanisms underlying these findings. Many of the reported genes were unknown to influence DNA methylation, resulting in a comprehensive resource providing insights in the principles underlying epigenetic regulation.

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Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data

Nucleic Acids Research ◽

10.1093/nar/gkz799 ◽

2019 ◽

Vol 47 (20) ◽

pp. 10580-10596 ◽

Cited By ~ 7

Author(s):

Karl J V Nordström ◽

Florian Schmidt ◽

Nina Gasparoni ◽

Abdulrahman Salhab ◽

Gilles Gasparoni ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Experimental Design ◽

Chromatin Accessibility ◽

Dnase I ◽

Open Chromatin ◽

Functional Interpretation ◽

Genome Wide ◽

Show Evidence

Abstract Chromatin accessibility maps are important for the functional interpretation of the genome. Here, we systematically analysed assay specific differences between DNase I-seq, ATAC-seq and NOMe-seq in a side by side experimental and bioinformatic setup. We observe that most prominent nucleosome depleted regions (NDRs, e.g. in promoters) are roboustly called by all three or at least two assays. However, we also find a high proportion of assay specific NDRs that are often ‘called’ by only one of the assays. We show evidence that these assay specific NDRs are indeed genuine open chromatin sites and contribute important information for accurate gene expression prediction. While technically ATAC-seq and DNase I-seq provide a superb high NDR calling rate for relatively low sequencing costs in comparison to NOMe-seq, NOMe-seq singles out for its genome-wide coverage allowing to not only detect NDRs but also endogenous DNA methylation and as we show here genome wide segmentation into heterochromatic B domains and local phasing of nucleosomes outside of NDRs. In summary, our comparisons strongly suggest to consider assay specific differences for the experimental design and for generalized and comparative functional interpretations.

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Genome-Wide DNA Methylation Comparison between Brassica napus Genic Male Sterile Line and Restorer Line

International Journal of Molecular Sciences ◽

10.3390/ijms19092689 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2689 ◽

Cited By ~ 6

Author(s):

Zhixin Wang ◽

Xiangping Wu ◽

Zengxiang Wu ◽

Hong An ◽

Bin Yi ◽

...

Keyword(s):

Dna Methylation ◽

Male Sterility ◽

Bisulfite Sequencing ◽

Epigenetic Modification ◽

Differentially Methylated Region ◽

Male Sterile ◽

Male Sterile Line ◽

Floral Buds ◽

Global Comparison ◽

Genome Wide

DNA methylation is an essential epigenetic modification that dynamically regulates gene expression during plant development. However, few studies have determined the DNA methylation profiles of male-sterile rapeseed. Here, we conducted a global comparison of DNA methylation patterns between the rapeseed genic male sterile line 7365A and its near-isogenic fertile line 7365B by whole-genome bisulfite sequencing (WGBS). Profiling of the genome-wide DNA methylation showed that the methylation level in floral buds was lower than that in leaves and roots. Besides, a total of 410 differentially methylated region-associated genes (DMGs) were identified in 7365A relative to 7365B. Traditional bisulfite sequencing polymerase chain reaction (PCR) was performed to validate the WGBS data. Eleven DMGs were found to be involved in anther and pollen development, which were analyzed by quantitative PCR. In particular, Bnams4 was hypo-methylated in 7365A, and its expression was up-regulated, which might affect other DMGs and thus control the male sterility. This study provided genome-wide DNA methylation profiles of floral buds and important clues for revealing the molecular mechanism of genic male sterility in rapeseed.

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Methylome modifications in monozygotic twins and in depression

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.854 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S30-S30

Author(s):

L. Fañanás ◽

A. Córdova-Palomera

Keyword(s):

Dna Methylation ◽

Monozygotic Twins ◽

Monozygotic Twin ◽

Epidemiological Studies ◽

P38 Map Kinase ◽

Biological Processes ◽

Genome Wide ◽

Glucocorticoid Signaling ◽

Analytical Strategies ◽

Competing Interest

Epigenetics is the study of gene expression changes that are produced by heritable, though potentially reversible, modifications of chromatin structure or DNA methylation. DNA methylation is interesting in epidemiological studies, due to its accessibility and since previous evidence indicates that large inter-individual differences in methylation levels at some loci may correlate with phenotypic plasticity in changing environments.Prior genome-wide methylomic research on depression has suggested that, together with differential DNA methylation changes, affected co-twins of monozygotic twin pairs have increased DNA methylation variability, probably in line with theories of epigenetic stochasticity. However, the putative biological roots of this variability remain largely unexplored.This study evaluate whether DNA methylation differences within MZ twin pairs were related to differences in their depressive status. Genome-wide DNA methylation levels were measured in peripheral blood of 34 twins (17 MZ pairs) using Illumina Infinium Human Methylation450 Beadchip. Two analytical strategies were used to identify differentially methylated probes (DMPs) and variably methylated probes (VMPs).The majority of the DMPs were located in genes previously related to neuropsychiatric phenotypes, such as WDR26, a GWAS hit for MDD whose expression levels have been found altered in blood of depressed individuals.VMPs were located in genes such as CACNA1C, IGF2 and the p38 MAP kinase MAPK11, showing enrichment for biological processes such as glucocorticoid signaling.The findings expand on previous research to indicate that both differential and variable methylation may play a role in the etiopathology of depression, and suggest specific genomic loci of potential interest in the epigenetics of depression.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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DNA methylome of the 20-gigabase Norway spruce genome

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1618019113 ◽

2016 ◽

Vol 113 (50) ◽

pp. E8106-E8113 ◽

Cited By ~ 39

Author(s):

Israel Ausin ◽

Suhua Feng ◽

Chaowei Yu ◽

Wanlu Liu ◽

Hsuan Yu Kuo ◽

...

Keyword(s):

Dna Methylation ◽

Somatic Embryogenesis ◽

Norway Spruce ◽

Biological Processes ◽

High Coverage ◽

Culture Cells ◽

Genome Wide ◽

Genome Bisulfite Sequencing ◽

Single Base Resolution ◽

Methylation Patterns

DNA methylation plays important roles in many biological processes, such as silencing of transposable elements, imprinting, and regulating gene expression. Many studies of DNA methylation have shown its essential roles in angiosperms (flowering plants). However, few studies have examined the roles and patterns of DNA methylation in gymnosperms. Here, we present genome-wide high coverage single-base resolution methylation maps of Norway spruce (Picea abies) from both needles and somatic embryogenesis culture cells via whole genome bisulfite sequencing. On average, DNA methylation levels of CG and CHG of Norway spruce were higher than most other plants studied. CHH methylation was found at a relatively low level; however, at least one copy of most of the RNA-directed DNA methylation pathway genes was found in Norway spruce, and CHH methylation was correlated with levels of siRNAs. In comparison with needles, somatic embryogenesis culture cells that are used for clonally propagating spruce trees showed lower levels of CG and CHG methylation but higher level of CHH methylation, suggesting that like in other species, these culture cells show abnormal methylation patterns.

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