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

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.

scholarly journals CG gene body DNA methylation changes and evolution of duplicated genes in cassava

2015 ◽  
Vol 112 (44) ◽  
pp. 13729-13734 ◽  
Author(s):  
Haifeng Wang ◽  
Getu Beyene ◽  
Jixian Zhai ◽  
Suhua Feng ◽  
Noah Fahlgren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Gene Copy ◽  
Gene Body ◽  
Duplicated Genes ◽  
Gene Body Methylation ◽  
Substantial Impact ◽  
Tropical Regions

DNA methylation is important for the regulation of gene expression and the silencing of transposons in plants. Here we present genome-wide methylation patterns at single-base pair resolution for cassava (Manihot esculenta, cultivar TME 7), a crop with a substantial impact in the agriculture of subtropical and tropical regions. On average, DNA methylation levels were higher in all three DNA sequence contexts (CG, CHG, and CHH, where H equals A, T, or C) than those of the most well-studied model plant Arabidopsis thaliana. As in other plants, DNA methylation was found both on transposons and in the transcribed regions (bodies) of many genes. Consistent with these patterns, at least one cassava gene copy of all of the known components of Arabidopsis DNA methylation pathways was identified. Methylation of LTR transposons (GYPSY and COPIA) was found to be unusually high compared with other types of transposons, suggesting that the control of the activity of these two types of transposons may be especially important. Analysis of duplicated gene pairs resulting from whole-genome duplication showed that gene body DNA methylation and gene expression levels have coevolved over short evolutionary time scales, reinforcing the positive relationship between gene body methylation and high levels of gene expression. Duplicated genes with the most divergent gene body methylation and expression patterns were found to have distinct biological functions and may have been under natural or human selection for cassava traits.

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

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.

scholarly journals Widespread natural variation of DNA methylation within angiosperms

2016 ◽  
Author(s):  
Chad E. Niederhuth ◽  
Adam J. Bewick ◽  
Lexiang Ji ◽  
Magdy S. Alabady ◽  
Kyung Do Kim ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Life Histories ◽  
Natural Variation ◽  
Gene Body ◽  
Sequencing Data ◽  
Gene Body Methylation ◽  
Genome Bisulfite Sequencing ◽  
Bisulfite Sequencing Data ◽  
Angiosperm Species ◽  
Methylation Patterns

AbstractTo understand the variation in genomic patterning of DNA methylation we compared methylomes of 34 diverse angiosperm species. By analyzing whole-genome bisulfite sequencing data in a phylogenetic context it becomes clear that there is extensive variation throughout angiosperms in gene body DNA methylation, euchromatic silencing of transposons and repeats, as well as silencing of heterochromatic transposons. The Brassicaceae have reduced CHG methylation levels and also reduced or loss of CG gene body methylation. The Poaceae are characterized by a lack or reduction of heterochromatic CHH methylation and enrichment of CHH methylation in genic regions. Reduced CHH methylation levels are found in clonally propagated species, suggesting that these methods of propagation may alter the epigenomic landscape over time. These results show that DNA methylation patterns are broadly a reflection of the evolutionary and life histories of plant species.

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

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.

scholarly journals DNA methylation affects pre-mRNA transcriptional initiation and processing in Arabidopsis

2021 ◽  
Author(s):  
Qiuhui Li ◽  
Shenjie Chen ◽  
Amy Wing-Sze Leung ◽  
Yaqin Liu ◽  
Yan Xin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Regulation Of Gene Expression ◽  
Mrna Processing ◽  
Intergenic Sequence ◽  
Whole Genome ◽  
Transcriptional Initiation ◽  
Whole Genome Bisulfite Sequencing ◽  
Genome Bisulfite Sequencing

Background: DNA methylation may regulate pre-mRNA transcriptional initiation and processing, thus affecting gene expression. Unlike animal cells, plants, especially Arabidopsis thaliana, have relatively low DNA methylation levels, limiting our ability to observe any correlation between DNA methylation and pre-mRNA processing using typical short-read sequencing. However, with newly developed long-read sequencing technologies, such as Oxford Nanopore Technology Direct RNA sequencing (ONT DRS), combined with whole-genome bisulfite sequencing, we were able to precisely analyze the relationship between DNA methylation and pre-mRNA transcriptional initiation and processing using DNA methylation-related mutants. Results: Using ONT DRS, we generated more than 2 million high-quality full-length long reads of native mRNA for each of the wild type Col-0 and mutants defective in DNA methylation, identifying a total of 117,474 isoforms. We found that low DNA methylation levels around splicing sites tended to prevent splicing events from occurring. The lengths of the poly(A) tail of mRNAs were positively correlated with DNA methylation. DNA methylation before transcription start sites or around transcription termination sites tended to result in gene-silencing or read-through events. Furthermore, using ONT DRS, we identified novel transcripts that we could not have otherwise, since transcripts with intron retention and fusion transcripts containing the uncut intergenic sequence tend not to be exported to the cytoplasm. Using the met1-3 mutant with activated constitutive heterochromatin regions, we confirmed the effects of DNA methylation on pre-mRNA processing. Conclusion: The combination of ONT DRS with whole-genome bisulfite sequencing was a powerful tool for studying the effects of DNA methylation on splicing site selection and pre-mRNA processing, and therefore regulation of gene expression.

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

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.

scholarly journals On the origin and evolutionary consequences of gene body DNA methylation

2016 ◽  
Vol 113 (32) ◽  
pp. 9111-9116 ◽  
Author(s):  
Adam J. Bewick ◽  
Lexiang Ji ◽  
Chad E. Niederhuth ◽  
Eva-Maria Willing ◽  
Brigitte T. Hofmeister ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Recombinant Inbred Lines ◽  
Dna Methyltransferases ◽  
Inbred Lines ◽  
Gene Body ◽  
Gene Body Methylation ◽  
Eutrema Salsugineum ◽  
And Function ◽  
Evolutionary Consequences

In plants, CG DNA methylation is prevalent in the transcribed regions of many constitutively expressed genes (gene body methylation; gbM), but the origin and function of gbM remain unknown. Here we report the discovery that Eutrema salsugineum has lost gbM from its genome, to our knowledge the first instance for an angiosperm. Of all known DNA methyltransferases, only CHROMOMETHYLASE 3 (CMT3) is missing from E. salsugineum. Identification of an additional angiosperm, Conringia planisiliqua, which independently lost CMT3 and gbM, supports that CMT3 is required for the establishment of gbM. Detailed analyses of gene expression, the histone variant H2A.Z, and various histone modifications in E. salsugineum and in Arabidopsis thaliana epigenetic recombinant inbred lines found no evidence in support of any role for gbM in regulating transcription or affecting the composition and modification of chromatin over evolutionary timescales.

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