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Koala methylomes reveal divergent and conserved DNA methylation signatures of X chromosome regulation.

ABSTRACT: X chromosome inactivation (XCI) mediated by differential DNA methylation between sexes is an iconic example of epigenetic regulation. Although XCI is shared between eutherians and marsupials, the role of DNA methylation in marsupial XCI remains contested. Here, we examine genome-wide signatures of DNA methylation across fives tissues from a male and female koala (Phascolarctos cinereus), and present the first whole-genome, multi-tissue marsupial 'methylome atlas'. Using these novel data, we elucidate divergent versus common features of representative marsupial and eutherian DNA methylation. First, tissue-specific differential DNA methylation in koalas primarily occurs in gene bodies. Second, females show significant global reduction (hypomethylation) of X chromosome DNA methylation compared to males. We show that this pattern is also observed in eutherians. Third, on average, promoter DNA methylation shows little difference between male and female koala X chromosomes, a pattern distinct from that of eutherians. Fourth, the sex-specific DNA methylation landscape upstream of Rsx, the primary lncRNA associated with marsupial XCI, is consistent with the epigenetic regulation of female-specific (and presumably inactive X chromosome-specific) expression. Finally, we use the prominent female X chromosome hypomethylation and classify 98 previously unplaced scaffolds as X-linked, contributing an additional 14.6 Mb (21.5%) to genomic data annotated as the koala X chromosome. Our work demonstrates evolutionarily divergent pathways leading to functionally conserved patterns of XCI in two deep branches of mammals.

SUBMITTER: Singh D

PROVIDER: S-EPMC7934952 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Koala methylomes reveal divergent and conserved DNA methylation signatures of X chromosome regulation

Project description:We examined genome-wide patterns of DNA methylation from whole genome DNA methylation maps of five tissues (brain, kidney, lung, skeletal muscle, and pancreas) from one male koala and one female koala (Phascolarctos cinereus), and present the first whole genome, multi-tissue “methylome atlas” with information on tissue- and sex-specific variation of DNA methylation for a marsupial.

2021-02-27 | GSE149600 | GEO

Koala methylomes reveal divergent and conserved DNA methylation signatures of X chromosome regulation

Project description:Koala methylomes reveal divergent and conserved DNA methylation signatures of X chromosome regulation

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Conserved and divergent patterns of DNA methylation in higher vertebrates.

Project description:DNA methylation in the genome plays a fundamental role in the regulation of gene expression and is widespread in the genome of eukaryotic species. For example, in higher vertebrates, there is a "global" methylation pattern involving complete methylation of CpG sites genome-wide, except in promoter regions that are typically enriched for CpG dinucleotides, or so called "CpG islands." Here, we comprehensively examined and compared the distribution of CpG sites within ten model eukaryotic species and linked the observed patterns to the role of DNA methylation in controlling gene transcription. The analysis revealed two distinct but conserved methylation patterns for gene promoters in human and mouse genomes, involving genes with distinct distributions of promoter CpGs and gene expression patterns. Comparative analysis with four other higher vertebrates revealed that the primary regulatory role of the DNA methylation system is highly conserved in higher vertebrates.

| S-EPMC4255770 | biostudies-literature

DNA methylation signatures reveal the diversity of processes remodeling liver cancer methylomes

Project description:Genome-scale DNA methylation was analyzed in a cohort of 239 hepatocellular adenomas and 35 normal liver tissues.

2020-09-03 | GSE157341 | GEO

DNA methylomes and transcriptomes analysis reveal implication of host DNA methylation machinery in BmNPV proliferation in Bombyx mori.

Project description:BACKGROUND:Bombyx mori nucleopolyhedrosis virus (BmNPV) is a major pathogen that threatens the sustainability of the sericultural industry. DNA methylation is a widespread gene regulation mode in epigenetics, which plays an important role in host immune response. Until now, little has been known about epigenetic regulation on virus diseases in insects. This study aims to explore the role of DNA methylation in BmNPV proliferation. RESULTS:Inhibiting DNA methyltransferase (DNMT) activity of silkworm can suppress BmNPV replication. The integrated analysis of transcriptomes and DNA methylomes in silkworm midguts infected with or without BmNPV showed that both the expression pattern of transcriptome and DNA methylation pattern are changed significantly upon BmNPV infection. A total of 241 differentially methylated regions (DMRs) were observed in BmNPV infected midguts, among which, 126 DMRs were hyper-methylated and 115 DMRs were hypo-methylated. Significant differences in both mRNA transcript level and DNA methylated levels were found in 26 genes. BS-PCR validated the hypermethylation of BGIBMGA014008, a structural maintenance of chromosomes protein gene in the BmNPV-infected midgut. In addition, DNMT inhibition reduced the expression of inhibitor of apoptosis family genes, iap1 from BmNPV, Bmiap2, BmSurvivin1 and BmSurvivin2. CONCLUSION:Our results indicate that DNA methylation plays positive roles in BmNPV proliferation and loss of DNMT activity could induce the apoptosis of infected cells to suppress BmNPV proliferation. Our results may provide a new idea and research direction for the molecular mechanism on insect-virus interaction.

| S-EPMC6792228 | biostudies-literature

Single-base-resolution methylomes of Populus trichocarpa reveal the association between DNA methylation and drought stress.

Project description:BackgroundDNA methylation is an important biological form of epigenetic modification, playing key roles in plant development and environmental responses.ResultsIn this study, we examined single-base resolution methylomes of Populus under control and drought stress conditions using high-throughput bisulfite sequencing for the first time. Our data showed methylation levels of methylated cytosines, upstream 2 kp, downstream 2kb, and repeatitive sequences significantly increased after drought treatment in Populus. Interestingly, methylation in 100 bp upstream of the transcriptional start site (TSS) repressed gene expression, while methylations in 100-2000 bp upstream of TSS and within the gene body were positively associated with gene expression. Integrated with the transcriptomic data, we found that all cis-splicing genes were non-methylated, suggesting that DNA methylation may not associate with cis-splicing. However, our results showed that 80% of trans-splicing genes were methylated. Moreover, we found 1156 transcription factors (TFs) with reduced methylation and expression levels and 690 TFs with increased methylation and expression levels after drought treatment. These TFs may play important roles in Populus drought stress responses through the changes of DNA methylation.ConclusionsThese findings may provide valuable new insight into our understanding of the interaction between gene expression and methylation of drought responses in Populus.

| S-EPMC4118614 | biostudies-literature

Divergent DNA Methylation Signatures of Juvenile Seedlings, Grafts and Adult Apple Trees.

Project description:The vast majority of previous studies on epigenetics in plants have centered on the study of inheritance of DNA methylation patterns in annual plants. In contrast, perennial plants may have the ability to accumulate changes in DNA methylation patterns over numerous years. However, currently little is known about long-lived perennial and clonally reproducing plants that may have evolved different DNA methylation inheritance mechanisms as compared to annual plants. To study the transmission of DNA methylation patterns in a perennial plant, we used apple (Malus domestica) as a model plant. First, we investigated the inheritance of DNA methylation patterns during sexual reproduction in apple by comparing DNA methylation patterns of mature trees to juvenile seedlings resulting from selfing. While we did not observe a drastic genome-wide change in DNA methylation levels, we found clear variations in DNA methylation patterns localized in regions enriched for genes involved in photosynthesis. Using transcriptomics, we also observed that genes involved in this pathway were overexpressed in seedlings. To assess how DNA methylation patterns are transmitted during clonal propagation we then compared global DNA methylation of a newly grafted tree to its mature donor tree. We identified significant, albeit weak DNA methylation changes resulting from grafting. Overall, we found that a majority of DNA methylation patterns from the mature donor tree are transmitted to newly grafted plants, however with detectable specific local differences. Both the epigenomic and transcriptomic data indicate that grafted plants are at an intermediate phase between an adult tree and seedling and inherit part of the epigenomic history of their donor tree.

| S-EPMC8594697 | biostudies-literature

Hodgkin Lymphoma Monozygotic Triplets Reveal Divergences in DNA Methylation Signatures.

Project description:We studied DNA methylation profiles in four different cell populations from a unique constellation of monozygotic triplets in whom two had developed Hodgkin Lymphoma (HL). We detected shared differences in DNA methylation signatures when comparing the two HL-affected triplets with the non-affected triplet. The differences were observed in naïve B-cells and marginal zone-like B-cells. DNA methylation differences were also detected when comparing each of the HL-affected triplets against each other. Even though we cannot determine whether treatment and/or disease triggered the observed differences, we believe our data are important on behalf of forthcoming studies, and that it might provide important clues for a better understanding of HL pathogenesis.

| S-EPMC7756121 | biostudies-literature

Dnmt2-dependent methylomes lack defined DNA methylation patterns.

Project description:Several organisms have retained methyltransferase 2 (Dnmt2) as their only candidate DNA methyltransferase gene. However, information about Dnmt2-dependent methylation patterns has been limited to a few isolated loci and the results have been discussed controversially. In addition, recent studies have shown that Dnmt2 functions as a tRNA methyltransferase, which raised the possibility that Dnmt2-only genomes might be unmethylated. We have now used whole-genome bisulfite sequencing to analyze the methylomes of Dnmt2-only organisms at single-base resolution. Our results show that the genomes of Schistosoma mansoni and Drosophila melanogaster lack detectable DNA methylation patterns. Residual unconverted cytosine residues shared many attributes with bisulfite deamination artifacts and were observed at comparable levels in Dnmt2-deficient flies. Furthermore, genetically modified Dnmt2-only mouse embryonic stem cells lost the DNA methylation patterns found in wild-type cells. Our results thus uncover fundamental differences among animal methylomes and suggest that DNA methylation is dispensable for a considerable number of eukaryotic organisms.

| S-EPMC3666705 | biostudies-literature

Genome-wide DNA methylomes from discrete developmental stages reveal the predominance of non-CpG methylation in Tribolium castaneum.

Project description:Cytosine DNA methylation is a vital epigenetic regulator of eukaryotic development. Whether this epigenetic modification occurs in Tribolium castaneum has been controversial, its distribution pattern and functions have not been established. Here, using bisulphite sequencing (BS-Seq), we confirmed the existence of DNA methylation and described the methylation profiles of the four life stages of T. castaneum. In the T. castaneum genome, both symmetrical CpG and non-CpG methylcytosines were observed. Symmetrical CpG methylation, which was catalysed by DNMT1 and occupied a small part in T. castaneum methylome, was primarily enriched in gene bodies and was positively correlated with gene expression levels. Asymmetrical non-CpG methylation, which was predominant in the methylome, was strongly concentrated in intergenic regions and introns but absent from exons. Gene body methylation was negatively correlated with gene expression levels. The distribution pattern and functions of this type of methylation were similar only to the methylome of Drosophila melanogaster, which further supports the existence of a novel methyltransferase in the two species responsible for this type of methylation. This first life-cycle methylome of T. castaneum reveals a novel and unique methylation pattern, which will contribute to the further understanding of the variety and functions of DNA methylation in eukaryotes.

| S-EPMC5737696 | biostudies-literature

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