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| Status |
Public on Sep 21, 2018 |
| Title |
The Zmiz1-Notch1 interaction induces Myc expression to drive steady state and stress thymopoiesis [ETP and DN3] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Notch1 signaling ramps up to very high levels in order to drive CD4-CD8- double-negative (DN) thymocytes to the CD4+CD8+ double-positive (DP) stage. During this important phase of T-cell development, which is known as the DN-DP transition, it is unclear whether the Notch1 complex simply strengthens its signal output as an isolated unit or recruits cofactors to amplify its signals. We previously showed that the PIAS-like coactivator Zmiz1 is a direct and context-dependent cofactor of Notch1 in T-cell leukemia. Using conditional knockout mouse models, we show that like inactivation of Notch, inactivation of Zmiz1 impaired the DN-DP transition under steady state and stress conditions. To determine mechanism, we performed RNA-Seq on sorted early T-lineage progenitor (ETP) and DN3 cells that were deprived of Zmiz1 signals either acutely (DeltaTamCre) or chronically (DeltaMxCre). To differentiate Notch1-independent from Notch1-dependent target genes, we also performed RNA-Seq on ETP and DN3 cells that were deprived of Notch1 signals using the anti-NRR Notch1 antibody. Our data suggests that Zmiz1 selectively amplifies a subset of Notch1 target genes in DN3 cells, such as Myc. In contrast, Zmiz1 does not have these functions in ETP cells, thus indicating stage-specific roles of Zmiz1.
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| Overall design |
RNA-Seq in murine ETP and DN3 thymocytes
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| |
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| Contributor(s) |
Wang Q, Chiang M, McEachin R |
| Citation(s) |
30076146 |
| |
| Submission date |
Jun 21, 2018 |
| Last update date |
Mar 19, 2019 |
| Contact name |
Richard C McEachin |
| E-mail(s) |
mceachin@umich.edu
|
| Organization name |
University of Michigan
|
| Department |
DCM&B
|
| Street address |
2800 Plymouth Road
|
| City |
Ann Arbor |
| State/province |
United States |
| ZIP/Postal code |
48109 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (40)
|
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| This SubSeries is part of SuperSeries: |
| GSE116125 |
The Zmiz1-Notch1 interaction induces Myc expression to drive steady state and stress thymopoiesis |
|
| Relations |
| BioProject |
PRJNA477331 |
| SRA |
SRP151034 |
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