Differential gene expression and genomic methylation profile of U937 cells transduced with WT/mutant-DNMT3A
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PROVIDER: PRJNA356398 | ENA |
REPOSITORIES: ENA
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Project description:DNA methyltransferase 3A (DNMT3A) gene is mutated in various myeloid neoplasms including acute myeloid leukemia (AML), especially at the Arg882 and associated with inferior outcomes. Despite the current progress of functional role of DNMT3A mutations, the molecular pathogenesis of myeloid malignancies remains poorly understood. The mechanisms of AML transformation and functional role of DNMT3A mutations through its target genes in the leukemogenesis remain to be explored. Here we wished to perform the differential genomic-methylation profile in U937 cells over-expressed with DNMT3A-Arg882His/Cys (R882H/C) mutations including DNMT3A-WT and vector using Illumina MethylationEPIC BeadChip microarray. Results: Differential genomic-methylation assess identified both hypo- and hypermethylation features in different regions throughout the whole genome of DNMT3A mutants-transduced U937 cells.
2017-12-01 | GSE90933 | GEO
Project description:DNA methyltransferase 3A (DNMT3A) gene is mutated in various myeloid neoplasms including acute myeloid leukemia (AML), especially at the Arg882 and associated with inferior outcomes. Despite the current progress of functional role of DNMT3A mutations, the molecular pathogenesis of myeloid malignancies remains poorly understood. The mechanisms of AML transformation and functional role of DNMT3A mutations through its target genes in the leukemogenesis remain to be explored. Here we wished to perform the differential gene expression profile in U937 cells over-expressed with DNMT3A-Arg882His/Cys (R882H/C) mutations including DNMT3A-WT and vector. Results: Gene expression profiling analysis revealed aberrant expression of several cell-cycle and apoptosis-related genes in U937 cells transduced with mutant DNMT3A compared to WT- or vector control.
2017-12-01 | GSE90931 | GEO
Project description:DNA methyltransferase 3A (DNMT3A) gene is mutated in various myeloid neoplasms including acute myeloid leukemia (AML), especially at the Arg882 and associated with inferior outcomes. Here we wished to perform the differential genomic-methylation profile in EOL-1 cells over-expressed with DNMT3A-Arg882Cys(R882C) and DNMT3A-Ser714Cys (S714C) mutations including DNMT3A-WT and vector. Results: Differential genomic-methylation assess identified both hypo- and hypermethylation features in different regions throughout the whole genome of DNMT3A mutants-transduced EOL-1 cells.
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Project description:Differential genomic-methylation profile of EOL-1 cells transduced with WT/mutant-DNMT3A
| PRJNA430692 | ENA
Project description:Despite the impact of DNMT3A mutation in acute myeloid leukemia has been emphasized, the precise molecular mechanisms in leukemogenesis are largely unknown. Here we show that, in murine transplantation experiments, recipients transplanted with DNMT3A mutant-transduced cells exhibit aberrant hematopoietic stem cell (HSC) accumulation. Differentiation-associated genes are down-regulated without accompanying changes in methylation status of their promoter-associated CpG islands in DNMT3A mutant-transduced stem/progenitor cells. DNMT3A mutant also promotes monoblastic transformation in vitro in combination with HOXA9. Molecularly, DNMT3A mutant interacts with polycomb repressive complex 1 (PRC1), leading to transcriptional silencing of PU.1. Suppression of PRC1 impairs aberrant HSC accumulation and monoblastic transformation. Taken together, our results highlight the functional role of DNMT3A mutation, forming the basis for leukemia development.
2016-02-10 | GSE55262 | GEO
Project description:Despite the impact of DNMT3A mutation in acute myeloid leukemia has been emphasized, the precise molecular mechanisms in leukemogenesis are largely unknown. Here we show that, in murine transplantation experiments, recipients transplanted with DNMT3A mutant-transduced cells exhibit aberrant hematopoietic stem cell (HSC) accumulation. Differentiation-associated genes are down-regulated without accompanying changes in methylation status of their promoter-associated CpG islands in DNMT3A mutant-transduced stem/progenitor cells. DNMT3A mutant also promotes monoblastic transformation in vitro in combination with HOXA9. Molecularly, DNMT3A mutant interacts with polycomb repressive complex 1 (PRC1), leading to transcriptional silencing of PU.1. Suppression of PRC1 impairs aberrant HSC accumulation and monoblastic transformation. Taken together, our results highlight the functional role of DNMT3A mutation, forming the basis for leukemia development. GFP-labeled empty vector, DNMT3A wild-type (WT), R882H-transduced LSK cells derived from transplanted mice were utilized for compared the expression profiles (3 sorted empty vector-transduced LSK cells, 3 sorted DNMT3A WT-transduced LSK cells, and 3 sorted DNMT3A R882H-transduced LSK cells. Total RNA was extracted by TaKaRa NucleoSpin RNA XS according to the manufacturerâs protocol. Amplification and biotin labeling of fragmented cDNA was carried out from 3.67 ng of total RNA by using NuGen Ovation Pico WTA System V2 (NuGEN) and SureTag Complete DNA Labeling Kit (Agilent). Each 2 μg of cDNA were hybridized to the Agilent SurePrint G3 Mouse Gene Expression 8x60K (Agilent) using Gene Expression Hybridization Kit (Agilent). After scanning, the signal intensity for each feature was measured by Agilent Feature Extraction (Agilent).
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Project description:Transcriptional profiling of mouse lung tumors comparing Dnmt3a KO/K-ras G12D mutant with Dnmt3a WT/K-ras G12D mutant. The goal is to search for the difference of mRNA abundance between Dnmt3a KO and WT tumors. Two-condition experiment, KO vs. WT tissure. Biological replicates: 12.
2011-10-25 | E-GEOD-32415 | biostudies-arrayexpress
Project description:Transcriptional profiling of mouse lung tumors comparing Dnmt3a KO/K-ras G12D mutant with Dnmt3a WT/K-ras G12D mutant. The goal is to search for the difference of mRNA abundance between Dnmt3a KO and WT tumors.
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