Photoperiodic stress induces genotype-specific shift in DNA methylation in Tartary
            buckwheat

Tartary buckwheat, known for its rich source of health beneficial secondary metabolites, is cultivated in many areas of the world. Among different environmental factors, photoperiod strongly influence its growth, flowering time, and ultimately the yield. In this context, epigenetics could contribute significantly in the regulation of plant response against changing environment. Therefore, with the aim to study the involvement of DNA methylation in photoperiod mediated plant response, genome-wide DNA methylation analysis was performed in two accessions (A1 and A2) of Tartary buckwheat using three photoperiodic treatments, i.e., 10-hr light/day (T1), 12-hr light/day (T2), and 14-hr light/day (T3). Flowering time and plant fresh weight data revealed that accessions A1 and A2 prefer T1 and T2 treatments, respectively. Total DNA methylation ratio increased with the increase in photoperiod in accession A1 but decreased under same conditions in accession A2. Full methylation increased significantly while intensive decrease in hemimethylation was noted from T2 to T3 in A1, whereas full methylation strongly increased and hemimethylation strongly decreased from T1 to T2 in A2. Overall, the DNA methylation events appeared more frequently than demethylation events. This study reports for the first time an accession-/genotype specific pattern of shift in the DNA methylation under different photoperiodic treatments that will pave the way toward identification of specific genes involved in the regulation of plant response against photoperiodic stress.

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PROSER1 mediates TET2 O-GlcNAcylation to regulate DNA demethylation on UTX-dependent enhancers and CpG islands

Life Science Alliance ◽

10.26508/lsa.202101228 ◽

2021 ◽

Vol 5 (1) ◽

pp. e202101228

Author(s):

Xiaokang Wang ◽

Wojciech Rosikiewicz ◽

Yurii Sedkov ◽

Tanner Martinez ◽

Baranda S Hansen ◽

...

Keyword(s):

Dna Methylation ◽

Target Genes ◽

Cpg Islands ◽

Dna Demethylation ◽

Dna Hypermethylation ◽

Genome Wide ◽

Associated Proteins ◽

Tet Enzymes ◽

Tet Protein ◽

First Time

DNA methylation at enhancers and CpG islands usually leads to gene repression, which is counteracted by DNA demethylation through the TET protein family. However, how TET enzymes are recruited and regulated at these genomic loci is not fully understood. Here, we identify TET2, the glycosyltransferase OGT and a previously undescribed proline and serine rich protein, PROSER1 as interactors of UTX, a component of the enhancer-associated MLL3/4 complexes. We find that PROSER1 mediates the interaction between OGT and TET2, thus promoting TET2 O-GlcNAcylation and protein stability. In addition, PROSER1, UTX, TET1/2, and OGT colocalize on many genomic elements genome-wide. Loss of PROSER1 results in lower enrichment of UTX, TET1/2, and OGT at enhancers and CpG islands, with a concomitant increase in DNA methylation and transcriptional down-regulation of associated target genes and increased DNA hypermethylation encroachment at H3K4me1-predisposed CpG islands. Furthermore, we provide evidence that PROSER1 acts as a more general regulator of OGT activity by controlling O-GlcNAcylation of multiple other chromatin signaling pathways. Taken together, this study describes for the first time a regulator of TET2 O-GlcNAcylation and its implications in mediating DNA demethylation at UTX-dependent enhancers and CpG islands and supports an important role for PROSER1 in regulating the function of various chromatin-associated proteins via OGT-mediated O-GlcNAcylation.

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Occupational exposure to pesticides is associated with differential DNA methylation

Occupational and Environmental Medicine ◽

10.1136/oemed-2017-104787 ◽

2018 ◽

Vol 75 (6) ◽

pp. 427-435 ◽

Cited By ~ 22

Author(s):

Diana A van der Plaat ◽

Kim de Jong ◽

Maaike de Vries ◽

Cleo C van Diemen ◽

Ivana Nedeljković ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Occupational Exposure ◽

Airway Obstruction ◽

Pesticide Exposure ◽

Airway Disease ◽

Disease Pathogenesis ◽

Genome Wide ◽

Wide Range ◽

First Time

ObjectivesOccupational pesticide exposure is associated with a wide range of diseases, including lung diseases, but it is largely unknown how pesticides influence airway disease pathogenesis. A potential mechanism might be through epigenetic mechanisms, like DNA methylation. Therefore, we assessed associations between occupational exposure to pesticides and genome-wide DNA methylation sites.Methods1561 subjects of LifeLines were included with either no (n=1392), low (n=108) or high (n=61) exposure to any type of pesticides (estimated based on current or last held job). Blood DNA methylation levels were measured using Illumina 450K arrays. Associations between pesticide exposure and 420 938 methylation sites (CpGs) were assessed using robust linear regression adjusted for appropriate confounders. In addition, we performed genome-wide stratified and interaction analyses by gender, smoking and airway obstruction status, and assessed associations between gene expression and methylation for genome-wide significant CpGs (n=2802).ResultsIn total for all analyses, high pesticide exposure was genome-wide significantly (false discovery rate P<0.05) associated with differential DNA methylation of 31 CpGs annotated to 29 genes. Twenty of these CpGs were found in subjects with airway obstruction. Several of the identified genes, for example, RYR1, ALLC, PTPRN2, LRRC3B, PAX2 and VTRNA2-1, are genes previously linked to either pesticide exposure or lung-related diseases. Seven out of 31 CpGs were associated with gene expression levels.ConclusionsWe show for the first time that occupational exposure to pesticides is genome-wide associated with differential DNA methylation. Further research should reveal whether this differential methylation plays a role in the airway disease pathogenesis induced by pesticides.

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A novel understanding of global DNA methylation in bobcat (Lynx rufus)

Genome ◽

10.1139/gen-2019-0046 ◽

2020 ◽

Vol 63 (2) ◽

pp. 125-130

Author(s):

Bonnie Cantrell ◽

Sydney Friedman ◽

Hannah Lachance ◽

Chris Bernier ◽

Brenda Murdoch ◽

...

Keyword(s):

Dna Methylation ◽

Conservation Biology ◽

Differential Methylation ◽

Lynx Rufus ◽

Global Dna Methylation ◽

Epigenetic Mechanisms ◽

Methylated Dna ◽

Genome Wide ◽

Weight Data ◽

Insight Into

Epigenetic mechanisms may provide a novel prospective of bobcat (Lynx rufus) adaptation to habitat loss/fragmentation. Previous research has focused on bobcat behavior and genetics, but epigenetics has not been studied in bobcat. The aim of this study was to determine the quantity of global DNA methylation in the liver of 30 bobcats. DNA was extracted from liver samples obtained from the Vermont Fish and Wildlife Department. The percent of global DNA methylation was quantified and calculated using the MethylFlashTM Methylated DNA 5-mC Quantification Kit from Epigentek (Farmingdale, NY, USA). Age, sex, and carcass weight data were collected at sampling and analyzed with percent of global DNA methylation. Global DNA methylation was found to range from 0.46% to 2.76%. Age ranged from <1 to 12 years old and weight ranged from 3.18 to 13.61 kg. Further analysis of differential methylation may provide insight into novel means of bobcat conservation within different regions of Vermont. These results reinforce the need for genome-wide epigenetic studies in conservation biology.

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Birth weight associations with psychiatric and physical health, cognitive function, and DNA methylation differences in an adult population

10.1101/664045 ◽

2019 ◽

Cited By ~ 6

Author(s):

Rebecca A. Madden ◽

Daniel L. McCartney ◽

Rosie M. Walker ◽

Robert F. Hillary ◽

Mairead L. Bermingham ◽

...

Keyword(s):

Dna Methylation ◽

Birth Weight ◽

Health Outcomes ◽

Data Linkage ◽

Meta Analysis ◽

Adult Health ◽

Adult Sample ◽

Genome Wide ◽

Plausible Mechanism ◽

Weight Data

AbstractBackgroundThe Developmental Origins of Adult Disease (DOAD) theory predicts that prenatal and early life events shape adult health outcomes. Birth weight is a useful indicator of the foetal experience, and has been associated with multiple adult health outcomes. DNA methylation (DNAm) is one plausible mechanism behind the relationship of birth weight to adult health.MethodsThe Generation Scotland study allows data linkage to historic Scottish birth cohorts, and birth records held through the NHS Information and Statistics Division. Data linkage with these sources yielded a sample of 4, 710 individuals. Health measures were related to birth weight in regression models. An epigenome-wide association study (EWAS) was performed in a subgroup (n=1, 395), relating adult DNAm from whole blood to birth weight, with replication in an independent sample (n=362). Associations between birth weight and epigenetic clocks were also assessed.FindingsHigher birth weight was significantly associated with reduced incidence of depression and osteoarthritis, higher body mass index, and higher general intelligence (absolute standardised effect size range 0·04 to 0·30, p(FDR)<0·05). Meta-analysis of discovery and replication EWAS studies yielded one genome-wide significant CpG site (p=5·97×10−9), cg00966482. Significant associations between birth weight and Grim Age (p=0·0014) and DNAm-derived telomere length (p=3·3×10−4) are also described.InterpretationOur results demonstrate associations between birth weight and adult health outcomes, with particularly striking effects for depression risk. It also provides support for an association between birth weight and DNAm, describing the first significant EWAS site associated with birth weight in an adult sample.FundingWellcome Trust Strategic Award 104036/Z/14/ZResearch in ContextEvidence before this studyThe associations between birth weight and various adult health outcomes have been well established. DNA methylation is a plausible mechanism through which early life experiences may continue to affect health throughout the lifecourse; however, evidence for birth weight associations with DNA methylation in adulthood has not yet been robustly established. This is likely due to small sample sizes of previous samples, as well as the use of poor-quality birth weight data, such as binary ‘low/normal’ variables or retrospective self-report. Alternatively, work has attempted to describe the persistence into adulthood of DNA methylation at sites identified at birth.Added value of this studyWe investigated genome-wide differential DNA methylation patterns from whole blood using data linkage-derived, continuous birth weight data, in the largest reported adult sample (n=1, 395) with replication (n=362) and meta-analysis. Meta-analysis revealed one epigenome-wide significant CpG site, to our knowledge the first significant EWAS result reported for birth weight in a an adult sample. In addition, we found associations between birth weight and GrimAge and a DNA methylation-derived measure of telomere length, demonstrating accelerated biological ageing in lower birth weight individuals. Together, these results suggest differential methylation exists in adulthood related to birth weight, and this may be relevant to health and mortality.Implications of all the available evidenceAlthough CpG sites differentially methylated with birth weight at parturition may not remain so throughout life, the adult epigenome may still provide information on the impact of birth weight on health outcomes. The adult epigenome, therefore, may represent a useful archive of the foetal experience which results in birth weight variability, and this information may provide clinically useful information in mid-life.

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Autopolyploidization in switchgrass alters phenotype and flowering time via epigenetic and transcription regulation

Journal of Experimental Botany ◽

10.1093/jxb/erz325 ◽

2019 ◽

Vol 70 (20) ◽

pp. 5673-5686 ◽

Cited By ~ 6

Author(s):

Haidong Yan ◽

Aureliano Bombarely ◽

Bin Xu ◽

Bingchao Wu ◽

Taylor P Frazier ◽

...

Keyword(s):

Dna Methylation ◽

Cell Division ◽

Flowering Time ◽

Panicum Virgatum ◽

Plant Evolution ◽

Cellulose Biosynthesis ◽

Auxin Response ◽

Phenotypic Changes ◽

First Time ◽

Growth And Reproduction

Abstract Polyploidization is a significant source of genomic and organism diversification during plant evolution, and leads to substantial alterations in plant phenotypes and natural fitness. To help understand the phenotypic and molecular impacts of autopolyploidization, we conducted epigenetic and full-transcriptomic analyses of a synthesized autopolyploid accession of switchgrass (Panicum virgatum) in order to interpret the molecular and phenotypic changes. We found that mCHH levels were decreased in both genic and transposable element (TE) regions, and that TE methylation near genes was decreased as well. Among 142 differentially expressed genes involved in cell division, cellulose biosynthesis, auxin response, growth, and reproduction processes, 75 of them were modified by 122 differentially methylated regions, 10 miRNAs, and 15 siRNAs. In addition, up-regulated PvTOE1 and suppressed PvFT probably contribute to later flowering time of the autopolyploid. The expression changes were probably associated with modification of nearby methylation sites and siRNAs. We also experimentally demonstrated that expression levels of PvFT and PvTOE1 were regulated by DNA methylation, supporting the link between alterations in methylation induced by polyploidization and the phenotypic changes that were observed. Collectively, our results show epigenetic modifications in synthetic autopolyploid switchgrass for the first time, and support the hypothesis that polyploidization-induced methylation is an important cause of phenotypic alterations and is potentially important for plant evolution and improved fitness.

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High-Resolution, Genome Wide Analysis of DNA Methylation Provides Insights Into the Epigenetic Architecture of t(4;14) Myeloma.

Blood ◽

10.1182/blood.v120.21.2385.2385 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2385-2385

Author(s):

Martin F Kaiser ◽

Brian A Walker ◽

Christopher P Wardell ◽

Fabio Mirabella ◽

Rosemary A Fryer ◽

...

Keyword(s):

Dna Methylation ◽

High Resolution ◽

Conflicts Of Interest ◽

Specific Pattern ◽

Binding Domain ◽

Regulatory Sequence ◽

Gene Promoters ◽

Dna Hypermethylation ◽

Methylation Array ◽

Genome Wide

Abstract Abstract 2385 The t(4;14) group in multiple myeloma (MM) is associated with a significantly impaired prognosis based on the overexpression of MMSET, a histone methyltransferase and epigenetic modifier that is thought to play a major role in myeloma genesis. We have previously shown that t(4;14) myelomas are associated with a specific pattern of DNA hypermethylation using Illumina HumanMethylation27 BeadChip arrays. These results were interpreted as being consistent with that MMSET overexpression leads to specific changes in the epigenetic architecture of MM. However, the detailed mechanism underlying this remains unclear partly due to the low resolution of methylation array technology used. In order to address this we have performed high-resolution genome-wide analyses of DNA methylation for t(4;14) and t(11;14) samples from patients with myeloma, plasma cell leukemia (PCL) and myeloma cell lines (HMCL) using methyl binding domain next generation sequencing (MBD-seq) in order to define DNA methylation patterns specific for t(4;14) MM, as well as to analyse methylation changes accompanying the progression from MM to PCL at a high-resolution, genome-wide scale. DNA from 6 myeloma patients at diagnosis [3 MM with t(4;14), 3 MM with t(11;14)], 6 patients with PCL [3 PCL with t(4;14), 3 PCL with t(11;14)] and 6 HMCL [3 with t(4;14), 3 non-t(4;14)] was fragmented. Methylated DNA fractions were captured using biotin-labelled methyl-binding domain 2 (MBD2) protein. Captured sequences bound to MBD were washed and eluted using elution buffers with increasing salt concentrations. Eluted fragments were purified and sequenced on an Illumina GAIIx, using 1.5 lanes per patient sample, generating 36 bp single-end reads. On average, 1.4 Gbases of reads were generated per sample. Sequences were aligned and de-duplicated using stampy and bwa algorithms. The reference genome (build hg19) was divided into overlapping bins of 200 bp (termed probes) and short read coverage per bin was normalised to per million reads aligned. Differentially methylated regions were defined by comparing normalised reads per probe between the t(4;14) and the t(11;14) groups for MM, PCL and HMCL groups. We first compared probe values that were higher in all three t(4;14) MM samples compared to the three t(11;14) samples. About 16500 probe values were higher in t(4,14) cases compared the t(11;14) group, whereas only 470 probes values were higher in all t(11;14) cases compared to t(4;14) cases. This confirms our previous observation that t(4;14) MM cases are characterised by pronounced hypermethylation. Of the 16500 probes values higher in t(4;14), about 9500 probes mapped to gene bodies and 600 to gene promoters, affecting in total about 1600 genes, indicating that gene or gene regulatory sequence hypermethylation is a common feature in t(4;14). Gene set enrichment analyses of these genes demonstrated highly significant enrichment of KEGG pathways ‘pathways in cancer’, ‘cell adhesion molecules’, the GO term ‘cell development’, among others, and an overrepresentation of probes mapping to chromosomal regions on chromosome 1q. When comparing the progression from MM to PCL, about 2600 genomic probe values were higher in all 3 t(11;14) PCL vs all 3 t(11;14) MM and 1600 probes in all 3 t(4;14) PCL vs MM, indicating that hypermethylation from MM to PCL is more pronounced in t(11;14) than in t(4;14). Very few differences in probe values were present when comparing all 6 MM (both t(4;14) and t(11;14)) with the 6 PCL samples, indicating that the epigenetic mechanisms involved in progression from MM to PCL might be different between the cytogenetic subgroups. Enrichment of methylated sequences was strong for both translocation groups when comparing PCLs with HMCLs, demonstrating that the epigenetic architecture of HMCLs differs significantly even from late-stage patient tumour material. This genome-wide methylation analysis provides us with candidate genes that are likely to be directly or indirectly epigenetically modified by MMSET. We are integrating this methylation data with gene expression data to identify expression-methylation correlations. Furthermore, additional experiments using MMSET knockout models will be used to further filter MMSET-specific effects on genome wide methylation. Finally, we go on to define epigenetic markers that could serve as biomarkers for future epigenetic therapies targeting epigenetic modifiers in t(4;14) myeloma. Disclosures: No relevant conflicts of interest to declare.

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Effects of Cadmium Sulfate on the Brown Garden Snail Cornu aspersum: Implications for DNA Methylation

Toxics ◽

10.3390/toxics9110306 ◽

2021 ◽

Vol 9 (11) ◽

pp. 306

Author(s):

Marius Georgescu ◽

George Andrei Drăghici ◽

Eliza-Florentina Oancea ◽

Cristina Adriana Dehelean ◽

Codruţa Şoica ◽

...

Keyword(s):

Dna Methylation ◽

Methylation Status ◽

Extensive Literature ◽

Dependent Manner ◽

Limited Data ◽

Cadmium Sulfate ◽

Genome Wide ◽

Cornu Aspersum ◽

Total Dna ◽

Dose Dependent

An extensive literature exists regarding the cellular, physiological, and genetic effects of cadmium (Cd)—A highly toxic, but commonly used trace metal in modern industry. However, limited data are available on its epigenetic effects, especially for terrestrial sentinel invertebrates. We determined Cd retention, total DNA methylation, and the methylation status of 5′ end of the Cd-MT gene in the hepatopancreas of the brown garden snail, Cornu aspersum, fed Cd sulfate for four weeks. Bodyweight changes and survival were also measured. Hepatopancreas cadmium increased in a dose-dependent manner from the third-lowest dose onward, with very large amounts being found for the highest treatment group. However, no mortalities occurred, irrespective of dietary Cd dose. We identified significant genome-wide hypermethylation in specimens given the highest dose, which overlapped with a significant bodyweight decrease. The Cd-MT gene showed an unmethylated 5′ end of the Cd-MT gene and this status was not affected by cadmium exposure. Hepatopancreas DNA methylation is as sensitive as bodyweight to non-lethal concentrations of dietary Cd given as cadmium sulfate but less responsive than tissue accumulation. Such an exposure event, by contrast, does not affect the methylation status of the Cd-MT gene 5′ end.

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