Global distribution of DNA hydroxymethylation and DNA methylation in chronic lymphocytic leukemia
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ABSTRACT:
PROVIDER: PRJNA450999 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7041540.fastq.gz | Fastqsanger.gz | |||
| SRR7041550.fastq.gz | Fastqsanger.gz | |||
| SRR7041560.fastq.gz | Fastqsanger.gz | |||
| SRR7041570.fastq.gz | Fastqsanger.gz | |||
| SRR7041580.fastq.gz | Fastqsanger.gz |
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Project description:We studied global distribution of hydroxymethylation (5hmC) and DNA methylation (5mC) in during normal B-cell development and CLL maturation. To derive disease-specific epigenetic changes we have compared CLL subgroups to their corresponding cell of origin. Our data showed that naïve B-cells, compared to non-class switched and class switched memory B-cells, had higher levels of 5-hmC and 5-mC. By comparing with ChIP sequencing data of H3K27Ac and H3K4me1 modifications of CLL samples with 5hmC and 5mC levels, we observed an increase of 5-hmC at overall gene body regions, CpG island shores and regulatory elements. Comparing 5-hmC distribution with RNA sequencing we showed that genes with higher transcriptional activity had higher 5-hmC and vice versa. Thus, our study suggests that the global loss of 5-hmC levels, with significant increase at gene regulatory regions, constitute a novel hallmark of CLL pathogenesis.
2019-01-23 | GSE113386 | GEO
Project description:BackgroundChronic lymphocytic leukemia (CLL) has been a good model system to understand the functional role of 5-methylcytosine (5-mC) in cancer progression. More recently, an oxidized form of 5-mC, 5-hydroxymethylcytosine (5-hmC) has gained lot of attention as a regulatory epigenetic modification with prognostic and diagnostic implications for several cancers. However, there is no global study exploring the role of 5-hydroxymethylcytosine (5-hmC) levels in CLL. Herein, using mass spectrometry and hMeDIP-sequencing, we analysed the dynamics of 5-hmC during B cell maturation and CLL pathogenesis.ResultsWe show that naïve B-cells had higher levels of 5-hmC and 5-mC compared to non-class switched and class-switched memory B-cells. We found a significant decrease in global 5-mC levels in CLL patients (n = 15) compared to naïve and memory B cells, with no changes detected between the CLL prognostic groups. On the other hand, global 5-hmC levels of CLL patients were similar to memory B cells and reduced compared to naïve B cells. Interestingly, 5-hmC levels were increased at regulatory regions such as gene-body, CpG island shores and shelves and 5-hmC distribution over the gene-body positively correlated with degree of transcriptional activity. Importantly, CLL samples showed aberrant 5-hmC and 5-mC pattern over gene-body compared to well-defined patterns in normal B-cells. Integrated analysis of 5-hmC and RNA-sequencing from CLL datasets identified three novel oncogenic drivers that could have potential roles in CLL development and progression.ConclusionsThus, our study suggests that the global loss of 5-hmC, accompanied by its significant increase at the gene regulatory regions, constitute a novel hallmark of CLL pathogenesis. Our combined analysis of 5-mC and 5-hmC sequencing provided insights into the potential role of 5-hmC in modulating gene expression changes during CLL pathogenesis.
| S-EPMC6322269 | biostudies-literature
Project description:X-Ray induced DNA-Hydroxymethylation changes
| PRJNA436999 | ENA
Project description:In this study we addressed the question whether changes of DNA hydroxymethylation after X-ray irradiation occur in a random fashion or if they show preferences for specific regions or features. We did not only focus on gene loci and promotor sights but also on gene body hydroxymethylation alterations and associated changes in gene expression. A more profound insight into hydroxymethylation characteristics triggered by radiation could provide clues to mechanisms and consequences of cellular response to irradiation including the immediate consequence of DNA strand breaks associated with active DNA demethylation as well as the long term risk of tumorigenesis or other associated diseases.
2019-01-29 | GSE111437 | GEO
Project description:Background: Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation marks by performing whole-genome next generation sequencing in representative normal and prostate cancer-derived cell lines in order to determine functional pathways and key genes regulated by these epigenomic modifications in cancer. Results: Our cell line model shows disruption of hydroxymethylation distribution in cancer, with global loss and highly specific gain in promoter and CpG island regions. Significantly, we observed locus-specific retention of hydroxymethylation marks in specific intronic and intergenic regions which may play a novel role in the regulation of gene expression in critical functional pathways, such as BARD1 signaling and steroid hormone receptor signaling in cancer. We confirm a modest correlation of hydroxymethylation with expression in intragenic regions in prostate cancer, while identifying an original role for intergenic hydroxymethylation in differentially expressed regulatory pathways in cancer. We also demonstrate a successful strategy for the identification and validation of key candidate genes from differentially regulated biological pathways in prostate cancer. Conclusion: Our results indicate a distinct function for aberrant hydroxymethylation within each genomic feature in cancer, suggesting a specific and complex role for the deregulation of hydroxymethylation in tumorigenesis, similar to methylation. Subsequently, our characterization of key cellular pathways exhibiting dynamic enrichment patterns for methylation and hydroxymethylation marks may allow us to identify differentially epigenetically modified target genes implicated in prostate cancer tumorigenesis. Methylation profiles of representative normal prostate cell line RWPE-1 and prostate adenocarcinoma cell line 22Rv1 were generated by MBD capture followed by high-throughput sequencing on the HiSeq 2500 (Illumina), in triplicate. Hydroxymethylation profiles of RWPE-1 and 22Rv1 were generated by hMeSeal followed by high-throughput sequencing on the HiSeq 2500 (one replicate each). Additional hydroxymethylation profiling for RWPE-1 was generated by hMeDIP followed by high-throughput sequencing on the HiSeq 2000 (Illumina).
2016-03-15 | E-GEOD-74464 | biostudies-arrayexpress
Project description:Our understanding of the posttranscriptional modifications that decorate RNA, a regulatory layer positioned between DNA and proteins, is in its infancy. Hydroxymethylcytosine, well described in DNA, occurs also in RNA, where its distribution, localization and function remain unexplored. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We provide the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and identify consensus sites for hydroxymethylation. We find that RNA hydroxymethylation can favor mRNA translation. Tet-deficient fruitflies show impaired brain development, accompanied by decreased RNA hydroxymethylation. Together, these steps into uncharted territory uncover central roles for RNA hydroxymethylation in Drosophila, highlighting the importance of epitranscriptomics.
2016-01-15 | GSE66090 | GEO
Project description:Background: Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation marks by performing whole-genome next generation sequencing in representative normal and prostate cancer-derived cell lines in order to determine functional pathways and key genes regulated by these epigenomic modifications in cancer. Results: Our cell line model shows disruption of hydroxymethylation distribution in cancer, with global loss and highly specific gain in promoter and CpG island regions. Significantly, we observed locus-specific retention of hydroxymethylation marks in specific intronic and intergenic regions which may play a novel role in the regulation of gene expression in critical functional pathways, such as BARD1 signaling and steroid hormone receptor signaling in cancer. We confirm a modest correlation of hydroxymethylation with expression in intragenic regions in prostate cancer, while identifying an original role for intergenic hydroxymethylation in differentially expressed regulatory pathways in cancer. We also demonstrate a successful strategy for the identification and validation of key candidate genes from differentially regulated biological pathways in prostate cancer. Conclusion: Our results indicate a distinct function for aberrant hydroxymethylation within each genomic feature in cancer, suggesting a specific and complex role for the deregulation of hydroxymethylation in tumorigenesis, similar to methylation. Subsequently, our characterization of key cellular pathways exhibiting dynamic enrichment patterns for methylation and hydroxymethylation marks may allow us to identify differentially epigenetically modified target genes implicated in prostate cancer tumorigenesis.
2016-03-15 | GSE74464 | GEO
Project description:Epigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We previously described dynamic changes in DNA methylation occurring during human fetal brain development, but other epigenetic processes operating during this period have not been extensively explored. Of particular interest is DNA hydroxymethylation (5hmC), a modification that is enriched in the human brain and hypothesized to play an important role in neuronal function, learning and memory. In this study, we quantify DNA hydroxymethylation across the genome of 71 human fetal brain samples spanning 23 to 184 days post-conception.
2017-08-25 | GSE94014 | GEO
Project description:The contribution of DNA methylation on the evolution of chronic lymphocytic leukemia has not been adequately studied yet. The purpose of this study was to investigate the role of DNA methylation in patients under chemoimmunotherapy. The overtime analysis of DNA methylation was performed on 40 patients in two time points: pre-treatment and after relapse, and 2 samples of memory B cells (MBC), using 450k arrays.
2019-12-10 | E-MTAB-7575 | biostudies-arrayexpress
Project description:DNA hydroxymethylation (5hmC) represents a new layer of epigenetic regulation in addition to DNA methylation (5mC). The genome-wide patterns of 5hmC distribution in many tissues and cells have recently been revealed by hydroxymethylated DNA immunoprecipitation (hMeDIP) followed by high throughput sequencing or tiling arrays. However, the DNA hydroxymethylome data generated by the conventional hMeDIP-seq method can not be used for direct quantitative comparison across different samples. In this study, we report a new quantitative hMeDIP-seq method, which uses barcode technology to label different DNA samples and performs hMeDIP-seq for multiple samples in one reaction system. Using this new method, we profiled and compared the DNA hydroxymethylomes of mouse ES cells (ESCs) and mouse ESCs-derived neural progenitor cells (NPCs). 5hmC levels around TSS in either ESCs or NPCs had negative correlation with gene expression levels，while 5hmC levels at gene body regions had different correlation with gene expression, depending on cell types. We identified differential hydroxymethylated regions (DHMRs) by comparing the 5hmC density of all 5hmC peaks between ESCs and NPCs. Many selected DHMRs (e.g., Ankrd23, Hist1h2aa, Fbxw7, and Epha2) were validated by hMeDIP-qPCR. Furthermore, we analyzed the relationship between the alteration of DNA hydroxymethylation and the gene expression change during neural differentiation, and our data suggest that both up- and down-regulated genes exhibited dramatic decrease in 5hmC during neural differentiation while the alteration of 5hmC had weak positive correlation with the changes in gene expression. Taken together, our data demonstrate that quantitative hMeDIP-seq is a powerful approach for genome-wide comparison of DNA hydroxymethylation across multiple samples. Importantly, the DHMRs between ESCs and NPCs uncovered in this study may provide clues for further investigation of the function of 5hmC in gene regulation and neural differentiation. Comparision of the genome-wide distribution of 5hmC in mouse embryonic stem cells and mouse ES-derived neural progenitor cells.
2013-03-08 | E-GEOD-40810 | biostudies-arrayexpress