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| Status |
Public on Nov 20, 2023 |
| Title |
Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
AML is a heterogenous disease caused by different mutations. We have previously shown that each mutational sub-type develops its specific gene regulatory network (GRN) with transcription factors interacting with multiple gene modules, many of which are transcription factor genes themselves. Here we hypothesized that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We tested this hypothesis using FLT3-ITD mutated AML as model and conducted an shRNA drop-out screen informed by this analysis. Our screen showed that AML-specific GRNs are predictive for identifying crucial regulatory modules required for AML but not normal cellular growth. Furthermore, our work shows that all modules are highly connected and regulate each other. The careful multi-omic analysis of the role of one (RUNX1) module by shRNA and chemical inhibition shows that this transcription factor and its target genes stabilize the GRN of FLT3-ITD AML and that its removal leads to GRN collapse and cell death
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| Overall design |
RUNX1 ChIP-Seq in FLT3-ITD primarly patient cells with CBFBi and control
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| Contributor(s) |
Keane P, Coleman D, Cockerill P, Bonifer C |
| Citation(s) |
38104314 |
| Submission date |
Jul 07, 2023 |
| Last update date |
Feb 19, 2024 |
| Contact name |
Peter Keane |
| E-mail(s) |
p.keane@bham.ac.uk
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| Organization name |
University of Birmingham
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| Department |
Institute for Cancer and Genomic Sciences
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| Street address |
Vincent Drive
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| City |
Birmingham |
| ZIP/Postal code |
B15 2TT |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE236775 |
Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth. |
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| Relations |
| BioProject |
PRJNA992411 |
