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Series GSE71473 Query DataSets for GSE71473
Status Public on Jun 23, 2016
Title Effect of DNMT3A R882H mutation or WT expression on global DNA methylation patterns of hematopoietic stem/progenitor cells with NRAS G12D co-transduction (eRRBS)
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary 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. 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.
 
Overall design 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.
 
Contributor(s) Lu R, Wang GG
Citation(s) 27344947
Submission date Jul 29, 2015
Last update date May 15, 2019
Contact name Rui Lu
E-mail(s) ruilu1@uabmc.edu
Organization name Univ of Alabama at Birmingham
Street address 1824 6th Ave S
City Birmingham
State/province AL
ZIP/Postal code 35294
Country USA
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (3)
GSM1835296 EV_RAS_eRRBS
GSM1835297 RH_RAS_eRRBS
GSM1835298 WT_RAS_eRRBS
This SubSeries is part of SuperSeries:
GSE71475 Epigenetic perturbations by Arg882-mutated DNMT3A potentiate aberrant stem cell gene expression program and acute leukemia development
Relations
BioProject PRJNA291346
SRA SRP061739

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE71473_RAW.tar 634.9 Mb (http)(custom) TAR (of BIGBED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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