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| Status |
Public on Sep 24, 2014 |
| Title |
Identification of a dynamic core transcriptional network in t(8;21) AML regulating differentiation block and self-renewal [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The leukemogenic fusion protein RUNX1/ETO impairs myeloid differentiation and drives malignant self-renewal. Here we use digital footprinting and ChIP-sequencing to identify the core RUNX1/ETO responsive transcriptional network of t(8;21) cells. We show that the transcriptional programme underlying leukemic propagation is regulated by a dynamic equilibrium between RUNX1/ETO and RUNX1 complexes, which bind in a mutually exclusive fashion to identical genomic sites. Perturbation of this equilibrium by RUNX1/ETO knockdown results in a global reassembly of transcription factor complexes within pre-existing open chromatin and the formation of a new C/EBP-alpha-dominated transcriptional network driving myeloid differentiation. Our work demonstrates that the block in myeloid differentiation in t(8;21) is caused by the dynamic balance between RUNX1/ETO and RUNX1 activities and the repression of C/EBP-alpha and highlights the core targets of epigenetic reprogramming in t(8;21) AML.
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| Overall design |
ChIP-sequencing and DNAse1-sequencing was used for the identification of a dynamic core transcriptional network in t(8;21) AML
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| Contributor(s) |
Ptasinska A, Assi SA, Piper J, Pickin A, Imperato MR, Hoogenkamp M, Cauchy P, Martinez-Soria N, James SR, Wu M, Ott S, Williamson D, Tenen DG, Westhead D, Cockerill P, Heidenreich O, Bonifer C |
| Citation(s) |
25242324 |
| Submission date |
Aug 05, 2014 |
| 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 (2) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE60131 |
Identification of a dynamic core transcriptional network in t(8;21) AML regulating differentiation block and self-renewal |
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| Relations |
| BioProject |
PRJNA257531 |
| SRA |
SRP045285 |
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