GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE87623 Query DataSets for GSE87623
Status Public on Jul 01, 2017
Title Vitamin C induced epigenomic remodeling in IDH1 mutant acute myeloid leukemia
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary The genomes of myeloid malignancies are characterized by epigenomic abnormalities. Heterozygous, inactivating TET2 mutations and neomorphic IDH mutations are recurrent and mutually exclusive in acute myeloid leukemia (AML) genomes. Ascorbic Acid (vitamin C) has been shown to stimulate the catalytic activity of TET2 in vitro and thus we sought to explore its effect in a leukemic model expressing IDH1R132H. Vitamin C treatment induced an IDH1R132H dependent reduction in cell proliferation and an increase in expression of genes involved in leukocyte differentiation. Vitamin C induced differentially methylated regions (DMRs) that displayed a significant overlap with enhancers implicated in myeloid differentiation and were enriched in sequence elements for the hematopoietic transcription factors RUNX1 and PU.1. ChIP-seq of PU.1 and RUNX1 revealed a significant loss of PU.1 and increase of RUNX1 bound DNA elements accompanied by their demethylation following vitamin C treatment. Additionally, vitamin C induced an increase in H3K27ac flanking sites bound by RUNX1. Based on these data we propose a model of vitamin C induced epigenetic remodelling of transcription factor binding sites driving differentiation in a leukemic model.
Overall design We describe the distribution of 5mC, 5hmC H3K4me1, H3K4me3, H3K27ac, Runx1 and PU.1 as well as the transcriptional profile of HOXA9 immortalized mouse bone marrow cells expressing IDH1 R132H mutant (and IDH1 wt for medip/hmedip)
Contributor(s) Mingay M, Hirst M
Citation(s) 28663574
Submission date Oct 05, 2016
Last update date May 15, 2019
Contact name Martin Hirst
Phone 604-822-6373
Organization name University of British Columbia
Department Department of Microbiology & Immunology
Street address 2125 East Mall
City Vancouver
State/province British Columbia
ZIP/Postal code V6T 1Z4
Country Canada
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (24)
GSM2335662 wt_unt_meDIPSeq
GSM2335663 wt_vitc_meDIPSeq
GSM2335664 mut_unt_meDIPSeq
BioProject PRJNA345426
SRA SRP090852

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
GSE87623_RAW.tar 1.8 Gb (http)(custom) TAR (of BED, TXT, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap