Invertebrate methylomes provide insight into mechanisms of environmental tolerance and reveal methodological biases

AbstractThere is a growing focus on the role of DNA methylation in the ability of marine invertebrates to rapidly respond to changing environmental factors and anthropogenic impacts. However, genome-wide DNA methylation studies in non-model organisms are currently hampered by limited understanding of methodological biases. Here we compare three methods for quantifying DNA methylation at single base pair resolution — Whole Genome Bisulfite Sequencing (WGBS), Reduced Representation Bisulfite Sequencing (RRBS), and Methyl-CpG Binding Domain Bisulfite Sequencing (MBDBS) — using multiple individuals from two reef-building coral species with contrasting environmental sensitivity. All methods reveal substantially greater methylation in Montipora capitata (11.4%) than the more sensitive Pocillopora acuta (2.9%). The majority of CpG methylation in both species occurs in gene bodies and flanking regions. In both species, MBDBS has the greatest capacity for detecting CpGs in coding regions at our sequencing depth, however MBDBS may be limited by intra-sample methylation heterogeneity. RRBS yields robust information for specific loci albeit without enrichment of any particular genome feature and with significantly reduced genome coverage. Relative genome size strongly influences the number and location of CpGs detected by each method when sequencing depth is limited, illuminating nuances in cross-species comparisons. These findings reinforce the role and importance of DNA methylation underlying environmental sensitivity in critical marine invertebrate taxa, and provide a genomic resource for investigating the functional role of DNA methylation in environmental tolerance.

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DNA Methylation and Transcriptomic Features are Preserved Throughout Disease Recurrence and Chemoresistance in High Grade Serous Ovarian Cancers

10.21203/rs.3.rs-1214611/v1 ◽

2022 ◽

Author(s):

Nicole Gull ◽

Michell Jones ◽

Pei-Chen Peng ◽

Simon Coetzee ◽

Tiago Silva ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Bisulfite Sequencing ◽

Disease Recurrence ◽

High Grade ◽

Chemotherapy Treatment ◽

Recurrent Tumors ◽

Genome Wide ◽

Genome Bisulfite Sequencing

Abstract Background Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). We performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with stage III/IV HGSOC, of which 11 patients carried germline, pathogenic BRCA1 and/or BRCA2 mutations. Results Landscapes of genome-wide methylation (on average 24.2 million CpGs per tumor) and transcriptomes in primary and recurrent tumors showed extensive heterogeneity between patients but were highly preserved in tumors from the same patient. We identified significant differences in the burden of differentially methylated regions (DMRs) in tumors from BRCA1/2 compared to non-BRCA1/2 carriers (mean 659 DMRs and 388 DMRs in paired comparisons respectively). We identified overexpression of immune pathways in BRCA1/2 carriers compared to non-carriers, implicating an increased immune response in improved survival (P=0.006) in these BRCA1/2 carriers. Conclusions These findings indicate methylome and gene expression programs established in the primary tumor are conserved throughout disease progression, even extensive chemotherapy treatment, and that changes in methylation and gene expression are unlikely to serve as drivers for chemoresistance in HGSOC.

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BoostMe accurately predicts DNA methylation values in whole-genome bisulfite sequencing of multiple human tissues

10.1101/207506 ◽

2017 ◽

Author(s):

Luli S. Zou ◽

Michael R. Erdos ◽

D. Leland Taylor ◽

Peter S. Chines ◽

Arushi Varshney ◽

...

Keyword(s):

Dna Methylation ◽

Bisulfite Sequencing ◽

Gradient Boosting ◽

Whole Genome ◽

Human Tissues ◽

Whole Genome Bisulfite Sequencing ◽

Genome Bisulfite Sequencing ◽

Boosting Algorithm ◽

Multiple Samples

AbstractBisulfite sequencing is widely employed to study the role of DNA methylation in disease; however, the data suffer from biases due to coverage depth variability. Here we describe BoostMe, a method for imputing low quality DNA methylation estimates within whole-genome bisulfite sequencing (WGBS) data. BoostMe uses a gradient boosting algorithm, XGBoost, and leverages information from multiple samples for prediction. We find that BoostMe outperforms existing algorithms in speed and accuracy when applied to WGBS of human tissues. We also show that imputation improves concordance between WGBS and the MethylationEPIC array at low WGBS depth, suggesting improved WGBS accuracy after imputation.

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Knockdown of Dnmt1 links Gene body DNA methylation to regulation of gene expression and maternal-zygotic transition in the wasp Nasonia

10.1101/2021.02.02.429402 ◽

2021 ◽

Author(s):

Deanna Arsala ◽

Xin Wu ◽

Soojin V. Yi ◽

Jeremy A. Lynch

Keyword(s):

Dna Methylation ◽

Bisulfite Sequencing ◽

Regulation Of Gene Expression ◽

Gene Body ◽

Nasonia Vitripennis ◽

Gene Body Methylation ◽

Genome Bisulfite Sequencing ◽

Genome Activation ◽

Zygotic Genome

AbstractGene body methylation (GBM) is an ancestral form of DNA methylation whose role in development has remained unclear. Unlike vertebrates, DNA methylation is found exclusively in gene bodies in the wasp Nasonia vitripennis, which provides a unique opportunity to interpret the role of GBM in development. We confirmed that parental RNAi (pRNAi) knockdown of a DNMT1 ortholog (Nv-Dnmt1a) in Nasonia leads to embryonic lethality and failures in cellularization and morphogenesis. Using whole-genome bisulfite sequencing, we found a widespread loss of GBM in Nv-Dnmt1a pRNAi embryos. Using RNAseq, we found that methylated genes that lost GBM in the pRNAi samples were exclusively downregulated during zygotic genome activation. Unexpectedly, nearly all affected unmethylated genes were up-regulated after pRNAi. Lack of proper clearance of mRNAs and abnormal activation drive this up-regulation, indicating critical roles for Nv-Dnmt1a and GBM in the maternal-zygotic transition (MZT) in the wasp, despite their absence in Drosophila.

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Benchmarking DNA Methylation Assays for Marine Invertebrates

10.1101/2020.02.10.943092 ◽

2020 ◽

Author(s):

Groves Dixon ◽

Mikhail Matz

Keyword(s):

Dna Methylation ◽

Bisulfite Sequencing ◽

Restriction Site ◽

Marine Invertebrates ◽

Cost Effective ◽

Whole Genome ◽

Ecological Research ◽

Chromatin Modifications ◽

Whole Genome Bisulfite Sequencing ◽

Genome Bisulfite Sequencing

AbstractInterrogation of chromatin modifications, such as DNA methylation, has potential to improve forecasting and conservation of marine ecosystems. The standard method for assaying DNA methylation (Whole Genome Bisulfite Sequencing), however, is too costly to apply at the scales required for ecological research. Here we evaluate different methods for measuring DNA methylation for ecological epigenetics. We compare Whole Genome Bisulfite Sequencing (WGBS) with Methylated CpG Binding Domain Sequencing (MBD-seq), and a modified version of MethylRAD we term methylation-dependent Restriction site-Associated DNA sequencing (mdRAD). We evaluate these three assays in measuring variation in methylation across the genome, between genotypes, and between polyp types in the reef-building coral Acropora millepora. We find that all three assays measure absolute methylation levels similarly, with tight correlations for methylation of gene bodies (gbM), as well as exons and 1Kb windows. Correlations for differential gbM between genotypes were weaker, but still concurrent across assays. We detected little to no reproducible differences in gbM between polyp types. We conclude that MBD-seq and mdRAD are reliable cost-effective alternatives to WGBS. Moreover, the considerably lower sequencing effort required for mdRAD to produce comparable methylation estimates makes it particularly useful for ecological epigenetics.

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Early Coastal Subsistence Patterns in Central Chile: A Systematic Study of the Marine-Invertebrate Fauna from the Site of Curaumilla-1

Latin American Antiquity ◽

10.2307/971929 ◽

1992 ◽

Vol 3 (1) ◽

pp. 43-62 ◽

Cited By ~ 46

Author(s):

Antonieta Jerardino ◽

Juan C. Castilla ◽

José Miguel Ramírez ◽

Nuriluz Hermosilla

Keyword(s):

Marine Invertebrates ◽

Marine Invertebrate ◽

Rocky Intertidal ◽

Present Species ◽

Central Chile ◽

Early Ceramic ◽

Minimum Number ◽

Minimum Number Of Individuals ◽

Number Of Individuals

Curaumilla-1 presents the earliest date for Archaic coastal occupation and marine exploitation in central Chile (8,500 years B. P.). The remains of marine invertebrates from this site at Punta Curaumilla were studied. The number of present species, minimum number of individuals for 14 species, and mean sizes of two of these species were established. Recent studies have demonstrated that modern shellfish gatherers are important modifiers of rocky-intertidal communities in central Chile. Consequently, we attempt here to define the probable ecological role of past people at Punta Curaumilla as shellfish gatherers. The molluscan species present at Curaumilla-1 are much the same as those exploited at present by shellfish gatherers in central Chile. Two pulses of occupation were identified within the Archaic and Early Ceramic periods respectively. During these events it is likely that Precolumbian people may have temporarily or permanently modified sectors of the rocky intertidal at Punta Curaumilla.

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Environment-driven reprogramming of gamete DNA methylation occurs during maturation and influences offspring fitness in salmon

10.1101/2020.11.25.396069 ◽

2020 ◽

Author(s):

Kyle Wellband ◽

David Roth ◽

Tommi Linnansaari ◽

R. Allen Curry ◽

Louis Bernatchez

Keyword(s):

Dna Methylation ◽

Early Life ◽

Bisulfite Sequencing ◽

Empirical Support ◽

Differential Methylation ◽

Transgenerational Plasticity ◽

Phenotypic Differences ◽

Genome Bisulfite Sequencing ◽

F1 Generation

AbstractAn epigenetic basis for transgenerational plasticity is widely theorized but convincing empirical support is limited by taxa-specific differences in the presence and role of epigenetic mechanisms. In teleost fishes, DNA methylation does not undergo extensive reprogramming and has been linked with environmentally-induced intergenerational effects, but solely in the context of early life environmental differences. Using whole genome bisulfite sequencing, we demonstrate that differential methylation of sperm occurs in response to captivity during maturation for Atlantic Salmon (Salmo salar), a species of major economic and conservation significance. We show that adult captive exposure further induces differential methylation in an F1 generation that is associated with fitness-related phenotypic differences. Gene targets of differential methylation are consistent with salmonid fishes experiencing early-life hatchery rearing as well as targets of selection in domesticated species. Our results support a mechanism of transgenerational plasticity mediated by intergenerational inheritance of DNA methylation acquired late in life for salmon.

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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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