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| Status |
Public on Jun 26, 2017 |
| Title |
RUNX1-ETO and RUNX1-EVI-1 differentially program the chromatin landscape in t(3;21) and t(8;21) AML but share global C/EBP-alpha dysfunction (DNase-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
RUNX1 is a frequent target of translocations in acute myeloid leukemia whereby its DNA binding domain fuses to different epigenetic regulators. To assess how different RUNX1 fusion proteins interact with the epigenome we compared the global binding patterns and the chromatin landscape of t(8;21) and t(3;21) AML which express RUNX1-ETO and RUNX1-EVI-1, respectively. We found that differential prognosis for these types of AML is reflected in fundamental differences in gene expression, chromatin landscape, binding patterns of the fusion proteins and other transcription factors as identified by genome-wide digital footprinting in patients. As previously shown for RUNX1-ETO, knockdown of RUNX1-EVI-1 expression initiates differentiation of t(3;21) cells which is associated with up-regulation of genes vital for myeloid differentiation, including C/EBPα. Furthermore, by expressing either dominant-negative C/EBP or an inducible C/EBPα construct in t(3;21) cells we show that C/EBPα is necessary and sufficient for the differentiation response of these cells to RUNX1-EVI-1 knockdown.
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| Overall design |
DNAse1-seq expreiments have been used to study the chromatin landscape of t(8;21) and t(3;21) AML
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| Contributor(s) |
Loke JC, Assi SA, Imperato MR, Ptasinska A, Cauchy P, Raghavan M, Delwel HR, Cockerill PN, Heidenreich O, Bonifer C |
| Citation(s) |
28538183 |
| Submission date |
Sep 22, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Salam Adli Assi |
| E-mail(s) |
s.a.assi@bham.ac.uk
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| 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 (6)
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| This SubSeries is part of SuperSeries: |
| GSE87286 |
RUNX1-ETO and RUNX1-EVI-1 differentially program the chromatin landscape in t(3;21) and t(8;21) AML but share global C/EBP-alpha dysfunction |
|
| Relations |
| BioProject |
PRJNA343969 |
| SRA |
SRP090332 |
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