Maximum DNA Methylation Fidelity in the Germline Tolerates Global Non-Functional Gene Body Methylation Dynamics During Development

2018 ◽  
Author(s):  
Assaf Zemach ◽  
James P. B. Lloyd ◽  
Keith D. Harris ◽  
Daniel Zilberman
Keyword(s):  
Dna Methylation ◽  
Functional Gene ◽  
Gene Body ◽  
Gene Body Methylation

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.

scholarly journals DNA methylation is not a driver of gene expression reprogramming in young honey bee workers

2021 ◽  
Author(s):  
Carlos A. M. Cardoso-Junior ◽  
Boris Yagound ◽  
Isobel Ronai ◽  
Emily J. Remnant ◽  
Klaus Hartfelder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Honey Bee ◽  
Differential Gene Expression ◽  
Social Contexts ◽  
Gene Body ◽  
Gene Body Methylation ◽  
Differential Gene ◽  
Honey Bee Workers ◽  
Methylation Patterns

AbstractIntragenic DNA methylation, also called gene body methylation, is an evolutionarily-conserved epigenetic mechanism in animals and plants. In social insects, gene body methylation is thought to contribute to behavioral plasticity, for example between foragers and nurse workers, by modulating gene expression. However, recent studies have suggested that the majority of DNA methylation is sequence-specific, and therefore cannot act as a flexible mediator between environmental cues and gene expression. To address this paradox, we examined whole-genome methylation patterns in the brains and ovaries of young honey bee workers that had been subjected to divergent social contexts: the presence or absence of the queen. Although these social contexts are known to bring about extreme changes in behavioral and reproductive traits through differential gene expression, we found no significant differences between the methylomes of workers from queenright and queenless colonies. In contrast, thousands of regions were differentially methylated between colonies, and these differences were not associated with differential gene expression in a subset of genes examined. Methylation patterns were highly similar between brain and ovary tissues and only differed in nine regions. These results strongly indicate that DNA methylation is not a driver of differential gene expression between tissues or behavioral morphs. Finally, despite the lack of difference in methylation patterns, queen presence affected the expression of all four DNA methyltransferase genes, suggesting that these enzymes have roles beyond DNA methylation. Therefore, the functional role of DNA methylation in social insect genomes remains an open question.

scholarly journals Epimutations are associated with CHROMOMETHYLASE 3-induced de novo DNA methylation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jered M Wendte ◽  
Yinwen Zhang ◽  
Lexiang Ji ◽  
Xiuling Shi ◽  
Rashmi R Hazarika ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Plant Species ◽  
Dna Methyltransferase ◽  
Constitutive Heterochromatin ◽  
De Novo ◽  
Flowering Plant ◽  
Gene Body ◽  
Gene Body Methylation ◽  
Mechanistic Basis ◽  
Flowering Plant Species

In many plant species, a subset of transcribed genes are characterized by strictly CG-context DNA methylation, referred to as gene body methylation (gbM). The mechanisms that establish gbM are unclear, yet flowering plant species naturally without gbM lack the DNA methyltransferase, CMT3, which maintains CHG (H = A, C, or T) and not CG methylation at constitutive heterochromatin. Here, we identify the mechanistic basis for gbM establishment by expressing CMT3 in a species naturally lacking CMT3. CMT3 expression reconstituted gbM through a progression of de novo CHG methylation on expressed genes, followed by the accumulation of CG methylation that could be inherited even following loss of the CMT3 transgene. Thus, gbM likely originates from the simultaneous targeting of loci by pathways that promote euchromatin and heterochromatin, which primes genes for the formation of stably inherited epimutations in the form of CG DNA methylation.

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 The Establishment of CDK9/ RNA PolII/H3K4me3/DNA Methylation Feedback Promotes HOTAIR Expression by RNA Elongation Enhancement in Cancer

2019 ◽  
Author(s):  
Chi Hin Wong ◽  
Chi Han Li ◽  
Qifang He ◽  
Joanna Hung Man Tong ◽  
Ka-Fai To ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cancer Progression ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Transcription Elongation ◽  
Underlying Mechanism ◽  
Transcriptional Elongation ◽  
Gene Body ◽  
Gene Body Methylation ◽  
Positive Feedback Loop

SUMMARYLong non-coding RNA HOX Transcript Antisense RNA (HOTAIR) is overexpressed in multiple cancers with diverse genetic profiles, which heavily contributed to cancer progression. However, the underlying mechanism leading to HOTAIR deregulation is largely unexplored. Here, we revealed that gene body methylation promoted HOTAIR expression through enhancing the transcription elongation process in cancer. We linked up the aberrant gene body histone and DNA methylation in promoting transcription elongation via phosphorylation of Polymerase II Ser 2 by CDK7-CDK9, and elucidated the mechanism of a positive feedback loop involving CDK7, MLL1 and DNMT3A in promoting gene body methylation and overexpressing HOTAIR. To our knowledge, this is the first time to demonstrate that a positive feedback loop that involved CDK9-mediated phosphorylation of PolII and histone and gene body methylation induced robust transcriptional elongation, which heavily contributed to the upregulation of oncogenic lncRNA in cancer.

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 Phylogenetic Shifts in Gene Body Methylation Correlate with Gene Expression and Reflect Trait Conservation

2019 ◽  
Vol 37 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Danelle K Seymour ◽  
Brandon S Gaut
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Evolution ◽  
Methylation Status ◽  
Evolutionary Constraint ◽  
Gene Body ◽  
Gene Body Methylation ◽  
Plant Genomes ◽  
Genome Wide ◽  
Rates Of Molecular Evolution

Abstract A subset of genes in plant genomes are labeled with DNA methylation specifically at CG residues. These genes, known as gene-body methylated (gbM), have a number of associated characteristics. They tend to have longer sequences, to be enriched for intermediate expression levels, and to be associated with slower rates of molecular evolution. Most importantly, gbM genes tend to maintain their level of DNA methylation between species, suggesting that this trait is under evolutionary constraint. Given the degree of conservation in gbM, we still know surprisingly little about its function in plant genomes or whether gbM is itself a target of selection. To address these questions, we surveyed DNA methylation across eight grass (Poaceae) species that span a gradient of genome sizes. We first established that genome size correlates with genome-wide DNA methylation levels, but less so for genic levels. We then leveraged genomic data to identify a set of 2,982 putative orthologs among the eight species and examined shifts of methylation status for each ortholog in a phylogenetic context. A total of 55% of orthologs exhibited a shift in gbM, but these shifts occurred predominantly on terminal branches, indicating that shifts in gbM are rarely conveyed over time. Finally, we found that the degree of conservation of gbM across species is associated with increased gene length, reduced rates of molecular evolution, and increased gene expression level, but reduced gene expression variation across species. Overall, these observations suggest a basis for evolutionary pressure to maintain gbM status over evolutionary time.

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 Phylogenetic shifts in gene body methylation correlate with gene expression and reflect trait conservation

2019 ◽  
Author(s):  
Danelle K. Seymour ◽  
Brandon S. Gaut
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Evolution ◽  
Methylation Status ◽  
Evolutionary Constraint ◽  
Gene Body ◽  
Gene Body Methylation ◽  
Plant Genomes ◽  
Genome Wide ◽  
Rates Of Molecular Evolution

ABSTRACTA subset of genes in plant genomes are labeled with DNA methylation specifically at CG residues. These genes, known as gene-body methylated (gbM), have a number of associated characteristics. They tend to have longer sequences, to be enriched for intermediate expression levels, and to be associated with slower rates of molecular evolution. Most importantly, gbM genes tend to maintain their level of DNA methylation between species, suggesting that this trait is under evolutionary constraint. Given the degree of conservation in gbM, we still know surprisingly little about its function in plant genomes or whether gbM is itself a target of selection. To address these questions, we surveyed DNA methylation across eight grass (Poaceae) species that span a gradient of genome sizes. We first established that genome size correlates with genome-wide DNA methylation levels, but less so for genic levels. We then leveraged genomic data to identify a set of 2,982 putative orthologs among the eight species and examined shifts of methylation status for each ortholog in a phylogenetic context. A total of 55% of orthologs exhibited a shift in gbM, but these shifts occurred predominantly on terminal branches, indicating that shifts in gbM are rarely conveyed over time. Finally, we found that the degree of conservation of gbM across species is associated with increased gene length, reduced rates of molecular evolution, and increased gene expression level, but reduced gene expression variation across species. Overall, these observations suggest a basis for evolutionary pressure to maintain gbM status over evolutionary time.

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