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Series GSE102697 Query DataSets for GSE102697
Status Public on Apr 30, 2018
Title C/EBPα overexpression overrides epigenetic reprogramming by RUNX1-ETO and RUNX1-EVI1 [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Acute myeloid leukemia (AML) is a heterogeneous disease caused by recurrent mutations in the transcription regulatory machinery. As a result, malignant myeloid cells display abnormal growth and are blocked in differentiation. One type of recurrent mutations affects RUNX1 which is subject to mutations and translocations, the latter giving rise to fusion proteins with aberrant transcriptional activities. We recently compared the mechanism by which the products of the t(8;21) and the t(3;21) translocation RUNX1-ETO and RUNX1-EVI1 globally reprogram the epigenome. We demonstrated that a main component of the block in differentiation in both types of AML is direct repression of the gene encoding for the crucial myeloid regulator C/EBPα by both fusion proteins. We also showed that CEBPA upregulation is required for the release of the differentiation block after oncogene knock-down. In the study presented here we examined at the global level the response of t(8;21) and t(3;21) cells to C/EBPα overexpression. We show that C/EBPα overexpression does not change oncoprotein expression or globally displace these proteins from their binding sites, but up-regulates a core set of common target genes important for myeloid differentiation and interferes with leukemic growth, highlighting CEBPA regulated pathways as targets for therapeutic intervention.
Overall design ChIP-seq experiments with inducible version of CEBPA (C/EBPα-ER) have been used to study the effect of CEBPA overexpression on transcription factor binding in t(8;21) and t(3;21) AML
Contributor(s) Loke J, Chin PS, Pickin A, Keane P, Assi SA, Ptasinska A, Imperato MR, Cockerill PN, Bonifer C
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Submission date Aug 15, 2017
Last update date May 15, 2019
Contact name Salam Adli Assi
Organization name University of Birmingham
Department Institute for Cancer and Genomic Sciences
Street address IBR
City Birmingham
ZIP/Postal code B15 2TT
Country United Kingdom
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (16)
GSM2743148 Evi1-SKH1-CEBPA-ER-E2_ChIPseq
GSM2743149 Evi1-SKH1-CEBPA-ER_ChIPseq
GSM2743150 Evi1-SKH1_ChIPseq
This SubSeries is part of SuperSeries:
GSE102742 C/EBPα overexpression overrides epigenetic reprogramming by RUNX1-ETO and RUNX1-EVI1
BioProject PRJNA398533
SRA SRP115568

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
GSE102697_RAW.tar 3.6 Gb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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