|
| Status |
Public on May 01, 2019 |
| Title |
Runx1 and Runx3 cooperatively repress Pmp22 to drive neurofibromagenesis [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Neurofibromatosis type 1 (NF1) patients are predisposed to develop neurofibromas but the underlying molecular mechanism(s) of neurofibromagenesis are not fully understood. We showed that dual genetic deletion of Runx1 (Rx1) and Runx3 (Rx3) in Schwann cells (SCs) and Schwann cell precursors (SCPs) significantly delayed neurofibromagenesis and prolonged mouse survival. We identified peripheral myelin protein 22 (Pmp22/Gas3) related to tumor initiation. Knockdown of Pmp22 with shRNAs increased Rx1fl/fl;Rx3fl/fl;Nf1fl/fl;DhhCre sphere numbers and enabled significantly more neurofibroma like micro-lesions on transplantation. Conversely, overexpression of Pmp22 in mouse neurofibroma SCs decreased proliferation. Mechanistically, Rx1/3 regulated alterative Pmp22 promoter usage and reduced post transcriptional expression of Pmp22. Finally, pharmacological inhibition of Runx/core binding factor beta (Cbf-β) activity significantly reduced neurofibroma volume in vivo. Thus, we identified a novel signaling pathway involving Rx1/3 suppression of Pmp22 in neurofibroma initiation and/or maintenance. Targeting disruption of Runx/Cbf-β interaction might provide a novel therapy for neurofibroma patients.
|
| |
|
| Overall design |
ChIP-seq on Runx-antibody treated sample and input DNA control sample
|
| |
|
| Contributor(s) |
Choi K, Wu J |
| Citation(s) |
31032403 |
| |
| Submission date |
Nov 20, 2018 |
| Last update date |
Mar 11, 2024 |
| Contact name |
Kwangmin Choi |
| Organization name |
Cincinnati Children's Hospital Medical Center
|
| Department |
Experimental Hematology & Cancer Biology
|
| Street address |
333 Burnet Avenue
|
| City |
Cincinnati |
| State/province |
Ohio |
| ZIP/Postal code |
45229 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (2) |
| GSM3484773 |
Nf1fl/fl;DhhCre neurofibroma cells_Input DNA |
| GSM3484774 |
Nf1fl/fl;DhhCre neurofibroma cells_RUNX1 antibody |
|
| This SubSeries is part of SuperSeries: |
| GSE122777 |
Runx1 and Runx3 cooperatively repress Pmp22 to drive neurofibromagenesis |
|
| Relations |
| BioProject |
PRJNA506268 |
| SRA |
SRP169968 |
