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| Status |
Public on Feb 19, 2019 |
| Title |
The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The Hippo pathway controls the activity of YAP/TAZ transcriptional coactivators through a kinase cascade. Despite the critical role of this pathway in tissue growth and tumorigenesis, it is not fully understood how YAP/TAZ–mediated transcription drives proliferation. By analyzing the effects of inactivating LATS1/2 kinases, the direct upstream inhibitors of YAP/TAZ, on mouse brain development and applying cell-number–normalized transcriptome analysis, we discovered that YAP/TAZ activation causes a global increase in transcription activity, known as hypertranscription, and upregulates many genes associated with increased biosynthetic capacity and proliferation. In contrast, conventional read-depth–normalized RNA-sequencing analysis failed to detect the scope of the transcriptome shift and missed most relevant gene ontologies. Hypertranscription in neural progenitors inhibits differentiation and triggers DNA replication stress, DNA damage, and p53 activation, resulting in massive apoptosis. Our findings reveal the remarkable impact of YAP/TAZ activation on global transcription activity and have important implications for understanding YAP/TAZ function.
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| |
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| Overall design |
H3K4me3 ChIP-seq comparing E12.5 control (no Cre) and Lats1/2;Nestin-Cre dKO mouse brains
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| |
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| Contributor(s) |
Lavado A, Kumar RP, Xu B, Fan Y, Neale G, Finkelstein D, Cao X |
| Citation(s) |
30523785 |
| Submission date |
Sep 16, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
David Finkelstein |
| E-mail(s) |
david.finkelstein@stjude.org
|
| Phone |
9014953931
|
| Organization name |
St Jude Children's Research Hospital
|
| Department |
Computational Biology
|
| Street address |
332 N. Lauderdale St.
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE120016 |
The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number |
|
| Relations |
| BioProject |
PRJNA491363 |
| SRA |
SRP161859 |
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