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| Status |
Public on Dec 14, 2020 |
| Title |
Different mutant RUNX1 oncoprotein classes program alternate hematopoietic differentiation trajectories [ATAC-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Mutations of the hematopoietic master regulator RUNX1 cause acute myeloid leukaemia, familial platelet disorder and other haematological malignancies whose phenotypes and prognoses depend on the class of RUNX1 mutation. The biochemical behavior of these oncoproteins and their ability to cause unique diseases has been well studied but the genomic basis of their differential action is unknown. To address this question we compared integrated phenotypic, transcriptomic and genomic data from cells expressing four types of RUNX1 oncoproteins in an inducible fashion during blood development from embryonic stem cells. We show that each class of RUNX1 mutation rapidly deregulates endogenous RUNX1 function by different mechanisms, leading to specific alterations in developmentally controlled transcription factor binding and chromatin programming. The result are distinct perturbations in the trajectories of gene regulatory network changes underlying blood cell development that are consistent with the nature of the final disease phenotype. The development of novel treatments for RUNX1-driven diseases will therefore require consideration beyond RUNX1 haploinsufficiency.
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| Overall design |
ATAC-Seq of mouse hematopietic progenitor cells expressing a doxycyclin inducible Runx1 oncoprotein construct. Samples include cells with and without doxycycline treatment.
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| Contributor(s) |
Kellaway S, Keane P, Edginton-White B, Kakkad R, Kennett E, Bonifer C |
| Citation(s) |
33397648 |
| |
| Submission date |
Jul 17, 2020 |
| Last update date |
Feb 01, 2021 |
| Contact name |
Peter Keane |
| E-mail(s) |
p.keane@bham.ac.uk
|
| Organization name |
University of Birmingham
|
| Department |
Institute for Cancer and Genomic Sciences
|
| Street address |
Vincent Drive
|
| City |
Birmingham |
| ZIP/Postal code |
B15 2TT |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE154623 |
Different mutant RUNX1 oncoprotein classes program alternate hematopoietic differentiation trajectories |
|
| Relations |
| BioProject |
PRJNA646875 |
| SRA |
SRP272343 |
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