scholarly journals Genome-Wide DNA Methylome and Whole-Transcriptome Landscapes of Spontaneous Intraductal Papilloma in Tree Shrews (Tupaia Belangeri)

2020 ◽  
Author(s):  
Chengxiu Liu ◽  
Yuanyuan Han ◽  
Pinfen Tong ◽  
Dexuan Kuang ◽  
Na Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Animal Model ◽  
Mammary Glands ◽  
Intraductal Papilloma ◽  
Whole Genome ◽  
Gene Body ◽  
Dna Methylome ◽  
Tree Shrews ◽  
Body Regions ◽  
Genome Wide

Abstract BackgroundBreast intraductal papilloma (IP) is mainly caused by the abnormal proliferation of ductal epithelial cells. Tree shrews are a potential animal model for studying breast tumours. However, little is known about the transcriptome and DNA methylome landscapes of breast IP in tree shrews. In this work, we performed whole-genome DNA methylation and transcriptome analyses of breast IPs and normal mammary glands in tree shrews.ResultsDNA methylation profiles with a single-base resolution were generated via whole-genome bisulphate sequencing (WGBS) in both the IP and Control groups of tree shrews. This provided a genome-wide perspective regarding the epigenetic regulation of protein-coding genes in breast IP in tree shrews. The methylation levels at CG sites were considerably higher than those at CHG and CHH sites, and methylation levels were highest in gene body regions. We identified 3486, 82 and 361 differentially methylated regions (DMRs) in CG, CHG, and CHH contexts, respectively, and 701 differentially methylated genes (DMGs) were found. Furthermore, transcriptomic analysis identified 62 differentially expressed genes (DEGs), 50 long noncoding RNAs (lncRNAs), and 32 circular RNAs (circRNAs) in IPs compared with normal mammary glands. Correlation analysis between the DNA methylation and transcriptome data showed that 25 DMGs were also DEGs, among which the expression levels of 9 genes were negatively correlated with methylation levels in gene body regions. Importantly, integrated analysis identified three genes, PDZK1, ATP2B4 and LCP1, that could be used as candidates for further studying breast IP in tree shrews.ConclusionsOverall, this research provides the comprehensive landscape of the transcriptome and DNA methylome of spontaneous IP in tree shrews and highlights candidate genes for eliciting tumorigenesis. These results contribute to the application of tree shrews as an animal model of breast tumours.

scholarly journals Genome-wide DNA methylome and whole-transcriptome landscapes of spontaneous intraductal papilloma in tree shrews

2021 ◽  
Vol 9 (8) ◽  
pp. 688-688
Author(s):  
Chengxiu Liu ◽  
Yuanyuan Han ◽  
Pinfen Tong ◽  
Dexuan Kuang ◽  
Na Li ◽  
...  
Keyword(s):  
Intraductal Papilloma ◽  
Dna Methylome ◽  
Tree Shrews ◽  
Genome Wide ◽  
Whole Transcriptome

scholarly journals Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles

2020 ◽  
Author(s):  
Benjamin I Laufer ◽  
Hyeyeon Hwang ◽  
Julia M Jianu ◽  
Charles E Mordaunt ◽  
Ian F Korf ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Down Syndrome ◽  
Early Life ◽  
Trisomy 21 ◽  
Bisulfite Sequencing ◽  
Dried Blood Spots ◽  
Whole Genome ◽  
Genome Wide ◽  
Low Pass ◽  
Genome Bisulfite Sequencing

Abstract Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example of genetics shaping epigenetics, as multiple array-based studies have demonstrated that trisomy 21 is characterized by genome-wide alterations to DNA methylation. By assaying over 24 million CpG sites, thousands of genome-wide significant (q < 0.05) differentially methylated regions (DMRs) that distinguished DS from typical development and idiopathic developmental delay were identified. Machine learning feature selection refined these DMRs to 22 loci. The DS DMRs mapped to genes involved in neurodevelopment, metabolism, and transcriptional regulation. Based on comparisons with previous DS methylation studies and reference epigenomes, the hypermethylated DS DMRs were significantly (q < 0.05) enriched across tissues while the hypomethylated DS DMRs were significantly (q < 0.05) enriched for blood-specific chromatin states. A ~28 kb block of hypermethylation was observed on chromosome 21 in the RUNX1 locus, which encodes a hematopoietic transcription factor whose binding motif was the most significantly enriched (q < 0.05) overall and specifically within the hypomethylated DMRs. Finally, we also identified DMRs that distinguished DS NDBS based on the presence or absence of congenital heart disease (CHD). Together, these results not only demonstrate the utility of low-pass WGBS on NDBS samples for epigenome-wide association studies, but also provide new insights into the early life mechanisms of epigenomic dysregulation resulting from trisomy 21.

scholarly journals Epigenetics of Animal Personality: DNA Methylation Cannot Explain the Heritability of Exploratory Behavior in a Songbird

2020 ◽  
Vol 60 (6) ◽  
pp. 1517-1530 ◽  
Author(s):  
Kees van Oers ◽  
Bernice Sepers ◽  
William Sies ◽  
Fleur Gawehns ◽  
Koen J F Verhoeven ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Exploratory Behavior ◽  
Parus Major ◽  
Phenotypic Selection ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Behavioral Differences ◽  
Heritable Variation ◽  
Genome Wide ◽  
Methylation Patterns

Synopsis The search for the hereditary mechanisms underlying quantitative traits traditionally focused on the identification of underlying genomic polymorphisms such as single-nucleotide polymorphisms. It has now become clear that epigenetic mechanisms, such as DNA methylation, can consistently alter gene expression over multiple generations. It is unclear, however, if and how DNA methylation can stably be transferred from one generation to the next and can thereby be a component of the heritable variation of a trait. In this study, we explore whether DNA methylation responds to phenotypic selection using whole-genome and genome-wide bisulfite approaches. We assessed differential erythrocyte DNA methylation patterns between extreme personality types in the Great Tit (Parus major). For this, we used individuals from a four-generation artificial bi-directional selection experiment and siblings from eight F2 inter-cross families. We find no differentially methylated sites when comparing the selected personality lines, providing no evidence for the so-called epialleles associated with exploratory behavior. Using a pair-wise sibling design in the F2 intercrosses, we show that the genome-wide DNA methylation profiles of individuals are mainly explained by family structure, indicating that the majority of variation in DNA methylation in CpG sites between individuals can be explained by genetic differences. Although we found some candidates explaining behavioral differences between F2 siblings, we could not confirm this with a whole-genome approach, thereby confirming the absence of epialleles in these F2 intercrosses. We conclude that while epigenetic variation may underlie phenotypic variation in behavioral traits, we were not able to find evidence that DNA methylation can explain heritable variation in personality traits in Great Tits.

scholarly journals Efficient and accurate determination of genome-wide DNA methylation patterns in Arabidopsis thaliana with enzymatic methyl sequencing

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Suhua Feng ◽  
Zhenhui Zhong ◽  
Ming Wang ◽  
Steven E. Jacobsen
Keyword(s):  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Accurate Determination ◽  
Gc Content ◽  
Epigenetic Mark ◽  
Whole Genome ◽  
Whole Genome Bisulfite Sequencing ◽  
Genome Wide ◽  
A Genome ◽  
Genome Bisulfite Sequencing

Abstract Background 5′ methylation of cytosines in DNA molecules is an important epigenetic mark in eukaryotes. Bisulfite sequencing is the gold standard of DNA methylation detection, and whole-genome bisulfite sequencing (WGBS) has been widely used to detect methylation at single-nucleotide resolution on a genome-wide scale. However, sodium bisulfite is known to severely degrade DNA, which, in combination with biases introduced during PCR amplification, leads to unbalanced base representation in the final sequencing libraries. Enzymatic conversion of unmethylated cytosines to uracils can achieve the same end product for sequencing as does bisulfite treatment and does not affect the integrity of the DNA; enzymatic methylation sequencing may, thus, provide advantages over bisulfite sequencing. Results Using an enzymatic methyl-seq (EM-seq) technique to selectively deaminate unmethylated cytosines to uracils, we generated and sequenced libraries based on different amounts of Arabidopsis input DNA and different numbers of PCR cycles, and compared these data to results from traditional whole-genome bisulfite sequencing. We found that EM-seq libraries were more consistent between replicates and had higher mapping and lower duplication rates, lower background noise, higher average coverage, and higher coverage of total cytosines. Differential methylation region (DMR) analysis showed that WGBS tended to over-estimate methylation levels especially in CHG and CHH contexts, whereas EM-seq detected higher CG methylation levels in certain highly methylated areas. These phenomena can be mostly explained by a correlation of WGBS methylation estimation with GC content and methylated cytosine density. We used EM-seq to compare methylation between leaves and flowers, and found that CHG methylation level is greatly elevated in flowers, especially in pericentromeric regions. Conclusion We suggest that EM-seq is a more accurate and reliable approach than WGBS to detect methylation. Compared to WGBS, the results of EM-seq are less affected by differences in library preparation conditions or by the skewed base composition in the converted DNA. It may therefore be more desirable to use EM-seq in methylation studies.

scholarly journals DNA Analysis by Restriction Enzyme (DARE) enables concurrent genomic and epigenomic characterization of single cells

2019 ◽  
Vol 47 (19) ◽  
pp. e122-e122
Author(s):  
Ramya Viswanathan ◽  
Elsie Cheruba ◽  
Lih Feng Cheow
Keyword(s):  
Dna Methylation ◽  
Restriction Enzyme ◽  
Copy Number ◽  
Dna Analysis ◽  
Whole Genome Amplification ◽  
Single Cells ◽  
Whole Genome ◽  
Copy Number Alterations ◽  
Genome Wide

Abstract Genome-wide profiling of copy number alterations and DNA methylation in single cells could enable detailed investigation into the genomic and epigenomic heterogeneity of complex cell populations. However, current methods to do this require complex sample processing and cleanup steps, lack consistency, or are biased in their genomic representation. Here, we describe a novel single-tube enzymatic method, DNA Analysis by Restriction Enzyme (DARE), to perform deterministic whole genome amplification while preserving DNA methylation information. This method was evaluated on low amounts of DNA and single cells, and provides accurate copy number aberration calling and representative DNA methylation measurement across the whole genome. Single-cell DARE is an attractive and scalable approach for concurrent genomic and epigenomic characterization of cells in a heterogeneous population.

Genome-wide DNA methylation profile of prepubertal porcine testis

2018 ◽  
Vol 30 (2) ◽  
pp. 349 ◽  
Author(s):  
Xi Chen ◽  
Liu-Hong Shen ◽  
Li-Xuan Gui ◽  
Fang Yang ◽  
Jie Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
High Throughput Sequencing ◽  
Cpg Islands ◽  
Methylation Profile ◽  
Testis Development ◽  
Body Regions ◽  
Genome Wide ◽  
Dna Methylation Profile ◽  
Mammalian Testis ◽  
Porcine Testis

The biological structure and function of the mammalian testis undergo important developmental changes during prepuberty and DNA methylation is dynamically regulated during testis development. In this study, we generated the first genome-wide DNA methylation profile of prepubertal porcine testis using methyl-DNA immunoprecipitation (MeDIP) combined with high-throughput sequencing (MeDIP-seq). Over 190 million high-quality reads were generated, containing 43 642 CpG islands. There was an overall downtrend of methylation during development, which was clear in promoter regions but less so in gene-body regions. We also identified thousands of differentially methylated regions (DMRs) among the three prepubertal time points (1 month, T1; 2 months, T2; 3 months, T3), the majority of which showed decreasing methylation levels over time. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that many genes in the DMRs were linked with cell proliferation and some important pathways in porcine testis development. Our data suggest that DNA methylation plays an important role in prepubertal development of porcine testis, with an obvious downtrend of methylation levels from T1 to T3. Overall, our study provides a foundation for future studies and gives new insights into mammalian testis development.

scholarly journals Cecum methylome response to Salmonella enterica serovar Enteritidis infection in chicken through whole genome bisulfite sequencing

2020 ◽  
Author(s):  
Yuanmei Wang ◽  
Liying Liu ◽  
Min Li ◽  
Lili Lin ◽  
Pengcheng Su ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Signaling Pathway ◽  
Salmonella Enterica ◽  
Bisulfite Sequencing ◽  
Whole Genome ◽  
Poultry Production ◽  
Whole Genome Bisulfite Sequencing ◽  
Genome Wide ◽  
Differentially Methylated Genes ◽  
Genome Bisulfite Sequencing

Abstract Background: Salmonella enterica serovar Enteritidis (SE) is one of the pathogenic bacteria, which affects poultry production and poses severe threat to public health. Chicken meat and egg are the main source of SE. DNA methylation, an important epigenetic modification, involves in regulatory processes including gene expression, chromatin structure and genomic imprinting. To understand the methylation regulation in response to SE inoculation in chicken, the genome-wide DNA methylation profile following SE inoculation was analyzed through whole genome bisulfite sequencing in the current study. Results: There were 185,362,463 clean reads and 126,098,724 unique reads in the control group, and 180,530,750 clean Reads, 126,782,896 unique reads in the inoculated group. We found that the methylation density in gene body was higher than that in the upstream and downstream regions of gene. There were 8,946 differentially methylated genes (3,639 hypo-methylated genes, 5,307 hyper-methylated genes) obtained between inoculated and control groups. Methylated genes were mainly enriched in immune-related Gene Ontology (GO) terms and metabolic process terms. Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, FoxO signaling pathway, Wnt signaling pathway and several metabolism-related pathways were significantly enriched. The density of differentially methylated cytosines in miRNAs was the highest. HOX genes were widely methylated and mainly distributed in Chr2 and 7. Conclusions: We firstly analyzed the genome-wide DNA methylation in the response to SE inoculation in chicken. SE inoculation promoted the DNA methylation in chicken cecum and caused methylation alteration in immune- and metabolic- related genes. Wnt signal pathway, miRNAs and HOX gene family may play a crucial role in the methylation regulation of SE infection in chicken. The findings herein will deepen the understanding of epigenetic regulation in the response to SE inoculation in chicken.

scholarly journals Genome-Wide DNA Methylation Variations Between Grass Carp with Different Ages

2020 ◽  
Author(s):  
Libo He ◽  
Denghui Zhu ◽  
Pengfei Chu ◽  
Yongming Li ◽  
Lanjie Liao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Immune Response ◽  
Grass Carp ◽  
Energy Production ◽  
Gene Body ◽  
Global Methylation ◽  
Genome Wide ◽  
Age Dependent ◽  
Different Ages

Abstract Background: Grass carp is an important farmed fish in China that infected by many pathogens, especially grass carp reovirus (GCRV). Notably, grass carp showed age-dependent susceptibility to GCRV, while the mechanism remains unclear. Herein, we performed a genome-wide survey of differences in DNA methylation and gene expression between five months old grass carp (FMO, sensitive to GCRV) and three years old grass carp (TYO, resistant to GCRV) aim to uncover the mechanism.Results: Colorimetric quantification revealed global methylation level of TYO fish was higher than that of FMO fish. Whole-genome bisulfite sequencing (WGBS) of two groups revealed 6,214 differentially methylated regions (DMRs) and 4,052 differentially methylated genes (DMGs), with most of DMRs and DMGs showed hypermethylation patterns in TYO fish. Correlation analysis indicated that DNA hypomethylation in promoter negative correlated with gene expression, whereas positive correlation was found between gene-body DNA hypermethylation and gene expression. Enrichment analysis revealed that promoter hypo-DMGs in TYO fish were significant enriched in pathways involved in immune response while gene-body hyper-DMGs in TYO fish were significant enriched in terms related to RNA transcription, biosynthetic, and energy production. RNA-seq indicated these terms or pathways involved in immune response, biosynthetic, and energy production also significant enriched for the up-regulated genes in TYO fish. Conclusions: Collectively, these results revealed the genome-wide DNA methylation variations between grass carp with different ages. DNA methylation and gene expression variations in genes involved in immune response, biosynthetic, and energy production may contributed to the age-dependent susceptibility to GCRV in grass carp. Our results will provide important information for the disease-resistant breeding programs of grass carp and may also benefit to the research of age-dependent diseases in human.

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