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| Status |
Public on Nov 01, 2016 |
| Title |
Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration [5hmC] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
In order to understand if early epigenetic mechanisms instruct the long-term behaviour of neural stem cells (NSCs) and their progeny, we examined the protein Uhrf1 as it is highly expressed in NSCs of the developing brain and rapidly downregulated upon differentiation. Conditional deletion of Uhrf1 in the developing cerebral cortex resulted in rather normal proliferation and neurogenesis but severe postnatal neurodegeneration. During development, deletion of Uhrf1 resulted in global DNA hypomethylation with a strong activation of the IAP family of endogenous retroviral elements, accompanied by an increase in hydroxy methyl cytosine. Downregulation of Tet enzymes rescued the IAP activation in Uhrf1 cKO cells, suggesting an antagonistic interplay between Uhrf1 and Tet on IAP regulation. As IAP upregulation persists into postnatal stages in the conditional Uhrf1 KO mice, our data show the lack of means to repress IAPs in differentiating neurons that normally never express Uhrf1. The high load of viral proteins and other transcriptional dysregulation ultimately lead to extensive postnatal neurodegeneration. Taken together, these data show that early developmental NSC factors can have long-term effects in neuronal differentiation and survival. Moreover, it highlights how specific the consequences of widespread changes in DNA methylation are for certain classes of retroviral elements.
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| |
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| Overall design |
5hmC analysis in control vs. Uhrf1-deficient brain
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| |
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| Contributor(s) |
Schotta G, Ramesh V, Götz M |
| Citation(s) |
27798843 |
| Submission date |
Jul 19, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Gunnar Schotta |
| E-mail(s) |
gunnar.schotta@bmc.med.lmu.de
|
| Phone |
089218075422
|
| Organization name |
LMU Munich
|
| Department |
Biomedical Center
|
| Street address |
Grosshaderner Strasse 9
|
| City |
Planegg-Martinsried |
| ZIP/Postal code |
82152 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE84550 |
Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration |
|
| Relations |
| BioProject |
PRJNA329590 |
| SRA |
SRP078909 |
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