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| Status |
Public on Sep 11, 2019 |
| Title |
Control of neural daughter cell proliferation by multi-level Notch/Su(H)/E(spl)HLH signaling. (PMID: 27070787) |
| Organism |
Drosophila melanogaster |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
We expressed DamID and Flag-tagged versions of E(spl)HLH-m5, -m8 and Su(H), in Drosophila embryos and analyzed their DNA-binding by DamID-seq and ChIP-seq.
The Notch pathway controls proliferation during development and in adulthood, and is frequently affected in many disorders. However, the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging. Here, we address the complexity of Notch signaling with respect to proliferation, using the developing Drosophila CNS as model. We find that a Notch/Su(H)/E(spl)-HLH cascade specifically controls daughter, but not progenitor proliferation. Additionally, we find that different E(spl)-HLH genes are required in different neuroblast lineages. The Notch/Su(H)/E(spl)-HLH cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21CIP1/p27KIP1/p57Kip2). ChIP and DamID analysis of Su(H) and E(spl)-HLH indicates direct transcriptional regulation of the cell cycle genes, and of the Notch pathway itself. These results point to a multi-level signaling model, and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems.
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| Overall design |
DamID-seq and ChIP-seq analysis of Drosophila melanogaster embryos, at developmental stage 9-16, expressing DamID and Flag-tagged versions of E(spl)HLH-m5, -m8 and Su(H)
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| Contributor(s) |
Thor S |
| Citation(s) |
27070787 |
| |
| Submission date |
Sep 10, 2019 |
| Last update date |
Sep 11, 2019 |
| Contact name |
Stefan Thor |
| E-mail(s) |
s.thor@uq.edu.au
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| Organization name |
University of Queensland
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| Department |
School of Biomedical Sciences
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| Lab |
Thor
|
| Street address |
Skerman Bldg (65) room 506
|
| City |
St Lucia |
| State/province |
QLD |
| ZIP/Postal code |
4072 |
| Country |
Australia |
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| Platforms (1) |
| GPL17275 |
Illumina HiSeq 2500 (Drosophila melanogaster) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA564789 |
| SRA |
SRP221244 |
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