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PROVIDER: PRJEB55802 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:High-resolution Nanopore methylome-maps reveal random hyper-methylation at CpG-poor regions as driver of chemoresistance in leukemias.
| PRJNA882066 | ENA
Project description:Gene expression of murine transposon-induced T cell acute lymphoblastic leukemias
| PRJEB59121 | ENA
Project description:The epigenome, including DNA methylation, is stably propagated during mitotic division. However, single-cell clonal expansion produces heterogeneous methylomes, raising the question of how the DNA methylome remains stable despite constant epigenetic drift. Here, we report that a clonal population of DNA (cytosine-5)-methyltransferase 1 (DNMT1)-only cells produces a heterogeneous methylome, which is robustly propagated on cell expansion and differentiation. Our data show that DNMT1 has imprecise maintenance activity and likely possesses weak de novo activity, leading to spontaneous ‘epimutations’. However, these epimutations tend to be corrected through a neighbor-guided mechanism, ikely enabled by environment-sensitive de novo activity (‘tuner’) and maintenance activity (‘stabilizer’) of DNMT1. By generating base-resolution maps of de novo and maintenance activities, we find that H3K9me2/3-marked regions show enhanced de novo activity, and CpG islands have both poor maintenance and de novo activities. The imprecise epigenetic machinery coupled with neighbor-guided correction may be a fundamental mechanism underlying robust yet flexible epigenetic inheritance.
2020-07-01 | GSE116482 | GEO
Project description:DNA methylation plays a vital role in genome dynamics and, in the human genome, occurs predominantly at cytosine guanine dinucleotide (CpG) sites. The diploid haploid human genome analysed here contains around 2060 million CpG sites (methylome) where DNA methylation can vary, affecting many biological processes in health and disease. Using whole-genome bisulfite sequencing, we report the essentially complete (92.6282%) methylome of human peripheral blood mononuclear cells (PBMC) which constitute an important source for clinical blood tests world-wide. We find the majority of CpG sites (68.4% at false positive rate of 0.46%) and only <0.2% of non-CpG sites to be methylated, demonstrating that non-CpG cytosine methylation is negligible in human PBMC. Analysis of the PBMC methylome revealed a rich landscape of epigenomic data for 20 distinct features including regulatory, protein-coding, RNA gene coding, non-coding and repeat sequences. Alu element mobility, for instance, was found to negatively correlate with their methylation levels, emphasizing the critical role of DNA methylation in genome stability. Integration of our methylome data with the previously determined genome sequence of the same Asian individual analysed here, enabled a first assessment of allele-specific methylation (ASM) differences between the two haploid methylomes of any individual. Using a conservative cut-off (p <0.001), we identified 599 haploid differentially methylated regions (hDMRs) covering 287 genes. Of these, 76 genes had hDMRs within 2kb of their transcriptional start sites of which >80% displayed allele-specific expression (ASE) after random testing using TA clone sequencing of the same PBMC sample. These data show, that ASM is a recurrent phenomenon and highly correlated with ASE, suggesting that imprinting may be more common than previously thought. Our study not only provides a comprehensive resource for future epigenomic research but also demonstrates a paradigm of large-scale epigenomics studies through new sequencing technology. We report the essentially complete (92.6282%) methylome of human peripheral blood mononuclear cells (PBMC) which constitute an important source for clinical blood tests world-wide.
2010-09-04 | E-GEOD-17972 | biostudies-arrayexpress
Project description:DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational âhotspotâ at Arg882 (DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. DNMT3A-R882H potentiates aberrant transactivation of âstemnessâ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. Mechanistically, R882-mutated DNMT3A directly binds to cis-regulatory elements of these genes and induces focal CpG hypomethylation reminiscent of what was seen in human leukemias bearing DNMT3A R882 mutation. Furthermore, DNMT3A-R882H induced DNA hypomethylation facilitates gene enhancer/promoter activation and recruitment of Dot1l-associated transcription elongation machineries. Inactivation of Dot1l represses DNMT3AR882H-mediated stem cell gene dysregulation and acute leukemogenicity. In this dataset, we provided enhanced Reduced Representation Bisulfite Sequencing (eRRBS) DNA methylome profiling data showing effect of DNMT3A R882H mutation or WT expression on hematopoietic stem/progenitor cells with NRAS G12D co-transduction. eRRBBs DNA methylome analysis of Lin- enriched hematopoietic stem/progenitor cells with retroviral infection of NRAS G12D alone (EV-RAS), DNMT3A R882H with NRAS G12D (RH-RAS) or DNMT3A WT with NRAS G12D (WT-RAS) at day 16 post-transduction.
2016-06-23 | E-GEOD-71473 | biostudies-arrayexpress
Project description:DNA methylation plays a vital role in genome dynamics and, in the human genome, occurs predominantly at cytosine guanine dinucleotide (CpG) sites. The diploid haploid human genome analysed here contains around 2060 million CpG sites (methylome) where DNA methylation can vary, affecting many biological processes in health and disease. Using whole-genome bisulfite sequencing, we report the essentially complete (92.6282%) methylome of human peripheral blood mononuclear cells (PBMC) which constitute an important source for clinical blood tests world-wide. We find the majority of CpG sites (68.4% at false positive rate of 0.46%) and only <0.2% of non-CpG sites to be methylated, demonstrating that non-CpG cytosine methylation is negligible in human PBMC. Analysis of the PBMC methylome revealed a rich landscape of epigenomic data for 20 distinct features including regulatory, protein-coding, RNA gene coding, non-coding and repeat sequences. Alu element mobility, for instance, was found to negatively correlate with their methylation levels, emphasizing the critical role of DNA methylation in genome stability. Integration of our methylome data with the previously determined genome sequence of the same Asian individual analysed here, enabled a first assessment of allele-specific methylation (ASM) differences between the two haploid methylomes of any individual. Using a conservative cut-off (p <0.001), we identified 599 haploid differentially methylated regions (hDMRs) covering 287 genes. Of these, 76 genes had hDMRs within 2kb of their transcriptional start sites of which >80% displayed allele-specific expression (ASE) after random testing using TA clone sequencing of the same PBMC sample. These data show, that ASM is a recurrent phenomenon and highly correlated with ASE, suggesting that imprinting may be more common than previously thought. Our study not only provides a comprehensive resource for future epigenomic research but also demonstrates a paradigm of large-scale epigenomics studies through new sequencing technology.
2010-09-04 | GSE17972 | GEO
Project description:Aberrant DNA-methylation at CpG dinucleotides is a hallmark of cancer and is associated with the emergence of resistance to anti-cancer treatment, though molecular mechanisms and biological signifi- cance remain elusive. Genome-scale methylation maps by currently used methods are based on chemical modification of DNA and are best suited for analyses of methylation at CpG-rich regions (CpG islands). We report the first high-coverage whole-genome map in cancer using the long-read nanopore technol- ogy, which allows simultaneous DNA-sequence and -methylation analyses on native DNA. We analyzed clonal epigenomic/genomic evolution in Acute Myeloid Leukemias (AMLs) at diagnosis and relapse, af- ter chemotherapy. Long-read sequencing coupled to a novel computational method allowed definition of differential methylation at unprecedented resolution (> 99% CpGs), extending analyses of CpG is- lands to sparse CpGs, which represent half of all differentially-methylated regions. We showed that the
2023-04-12 | GSE213685 | GEO
Project description:Aberrant DNA-methylation at CpG dinucleotides is a hallmark of cancer and is associated with the emergence of resistance to anti-cancer treatment, though molecular mechanisms and biological signifi- cance remain elusive. Genome-scale methylation maps by currently used methods are based on chemical modification of DNA and are best suited for analyses of methylation at CpG-rich regions (CpG islands). We report the first high-coverage whole-genome map in cancer using the long-read nanopore technol- ogy, which allows simultaneous DNA-sequence and -methylation analyses on native DNA. We analyzed clonal epigenomic/genomic evolution in Acute Myeloid Leukemias (AMLs) at diagnosis and relapse, af- ter chemotherapy. Long-read sequencing coupled to a novel computational method allowed definition of differential methylation at unprecedented resolution (> 99% CpGs), extending analyses of CpG is- lands to sparse CpGs, which represent half of all differentially-methylated regions. We showed that the
2023-04-12 | GSE213684 | GEO