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| 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
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| 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.
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| 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
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| Contributor(s) |
Loke J, Chin PS, Pickin A, Keane P, Assi SA, Ptasinska A, Imperato MR, Cockerill PN, Bonifer C |
| Citation missing |
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| Submission date |
Aug 15, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Salam Adli Assi |
| E-mail(s) |
s.a.assi@bham.ac.uk
|
| 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 |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE102742 |
C/EBPα overexpression overrides epigenetic reprogramming by RUNX1-ETO and RUNX1-EVI1 |
|
| Relations |
| BioProject |
PRJNA398533 |
| SRA |
SRP115568 |
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