GEO DataSets

(Submitter supplied) DNA methyltransferases DNMT3A- and DNMT3B-mediated de novo DNA methylation critically regulates epigenomic and transcriptomic patterning during development. The hotspot DNMT3A mutations at the site of Arg822 (R882) promote macro-oligomer formation, leading to aberrant DNA methylation that in turn contributes to pathogenesis of acute myeloid leukemia (AML). However, the molecular basis underlying the hotspot mutation-induced functional mis-regulation of DNMT3A remains unclear. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21697

15 Samples

Download data: BW, XLSX

(Submitter supplied) DNA methyltransferases DNMT3A- and DNMT3B-mediated de novo DNA methylation critically regulates epigenomic and transcriptomic patterning during development. The hotspot DNMT3A mutations at the site of Arg822 (R882) promote macro-oligomer formation, leading to aberrant DNA methylation that in turn contributes to pathogenesis of acute myeloid leukemia (AML). However, the molecular basis underlying the hotspot mutation-induced functional mis-regulation of DNMT3A remains unclear. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL21145

32 Samples

Download data: IDAT, TXT

(Submitter supplied) Although the majority of acute myeloid leukemia (AML) patients initially respond to chemotherapy, most of them subsequently relapse due to persistent, chemoresistant disease. However, the mechanistic basis by which AML cells persist during chemotherapy has not been fully delineated. Recurrent somatic mutations in the DNA methyltransferase 3A gene (DNMT3A), most frequently at arginine 882 (DNMT3Amut), are commonly observed in AML patients, and are also detected in elderly subjects with clonal hematopoiesis in the absence of leukemic transformation. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL17021

9 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

24 Samples

Download data: BW, TXT

(Submitter supplied) Although the majority of acute myeloid leukemia (AML) patients initially respond to chemotherapy, most of them subsequently relapse due to persistent, chemoresistant disease. However, the mechanistic basis by which AML cells persist during chemotherapy has not been fully delineated. Recurrent somatic mutations in the DNA methyltransferase 3A gene (DNMT3A), most frequently at arginine 882 (DNMT3Amut), are commonly observed in AML patients, and are also detected in elderly subjects with clonal hematopoiesis in the absence of leukemic transformation. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: BW

(Submitter supplied) Although the majority of acute myeloid leukemia (AML) patients initially respond to chemotherapy, most of them subsequently relapse due to persistent, chemoresistant disease. However, the mechanistic basis by which AML cells persist during chemotherapy has not been fully delineated. Recurrent somatic mutations in the DNA methyltransferase 3A gene (DNMT3A), most frequently at arginine 882 (DNMT3Amut), are commonly observed in AML patients, and are also detected in elderly subjects with clonal hematopoiesis in the absence of leukemic transformation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

9 Samples

Download data: CSV

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies. We report that DNMT3A mutational ‘hotspot’ at Arg882 (i.e., DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. Mechanistically, DNMT3A-R882H induced DNA hypomethylation facilitates gene enhancer/promoter activation. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL17400

4 Samples

Download data: CEL

(Submitter supplied) Mutation of DNA methyltransferase 3A at arginine 882 (DNMT3AR882mut) is prevalent in various hematological cancers. DNMT3AR882mut was recently shown to carry partially defective, dominant-negative or gain-of-function activities under different in vitro contexts. However, the causal roles for such a multifaceted effect of DNMT3AR882mut on leukemogenesis remain undefined. Here we report TF-1 leukemia cells as a robust system for modeling DNMT3AR882mut-dependent cell transformation phenotypes and for performing structure-function relationship studies of DNMT3AR882mut. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

35 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Third-party reanalysis; Methylation profiling by high throughput sequencing

Platform:

GPL11154

126 Samples

Download data: TXT

(Submitter supplied) Aberrant DNA methylation of gene promoters is a hallmark of AML. To define more precisely how cytosine methylation is redistributed in AML, we performed base-pair resolution methylome sequencing in 119 patients. We find that leukemic DNA methylation patterning is tightly linked to somatic mutations and primarily driven by regulatory elements outside of promoters and by CpG shores as opposed to CpG islands. more...

Organism:

Homo sapiens; Mus musculus

Type:

Methylation profiling by high throughput sequencing; Third-party reanalysis

Platform:

GPL11154

7 Samples

Download data: BED, TXT

(Submitter supplied) Aberrant DNA methylation of gene promoters is a hallmark of AML. To define how cytosine methylation is redistributed in AML more precisely we performed base-pair resolution methylome sequencing in 119 patients. We find that leukemic DNA methylation patterning is tightly linked to somatic mutations and primarily driven by regulatory elements outside of promoters and by CpG shores as opposed to CpG islands. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL11154

119 Samples

Download data: TXT

(Submitter supplied) DNA methyltransferase 3A (DNMT3A) is frequently mutated in hematological cancers; however, the underlying oncogenic mechanism remains elusive. Here, we report that DNMT3A mutational hotspot at Arg882 (DNMT3A R882H) cooperates with NRAS mutation to transform hematopoietic stem/progenitor cells and induce acute leukemia development. Mechanistically, DNMT3A R882H directly binds to and potentiates transactivation of stemness genes critical for leukemogenicity including Meis1, Mn1 and Hoxa gene cluster. more...

Organism:

Mus musculus

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platforms:

GPL17400 GPL1261 GPL13112

46 Samples

Download data: BEDGRAPH, BIGBED, CEL

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ 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 ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: BEDGRAPH

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ 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 ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL13112

3 Samples

Download data: BIGBED

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ 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 ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

13 Samples

Download data: BEDGRAPH

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ 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 ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

10 Samples

Download data: CEL

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ at Arg882 (i.e., 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 ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL17400

12 Samples

Download data: CEL

(Submitter supplied) Mammalian DNA methylation patterns are established by two de novo DNA methyltransferases DNMT3A and DNMT3B, which exhibit both redundant and distinctive methylation activities. However, the related molecular basis remains undetermined. Through comprehensive structural, enzymology and cellular characterizations of DNMT3A and DNMT3B, here we uncovered distinct and interrelated modes-of-action underlying their CpG site and flanking sequence interaction. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL21103

12 Samples

Download data: BIGWIG, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Methylation profiling by array; Methylation profiling by high throughput sequencing

Platforms:

GPL13534 GPL11154

70 Samples

Download data: TXT

(Submitter supplied) Whole genome bisulphite sequencing of 2 human cancer cell line samples. One cell line harbours a heterozygous mutation in the DNA methyl-transferase DNMT3a, a common alteration observed in AML patients. The main goal is to find the differentially methylated regions (DMR) at genome-wide level between the mutant and a wild-type cell lines to elucidate the effect of the mutation and the implication in leukomogenesis.

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL11154

2 Samples

Download data: TXT