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Series GSE84544 Query DataSets for GSE84544
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.
Overall design 5hmC analysis in control vs. Uhrf1-deficient brain
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
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)
GSM2241711 GS21-Het_prog_input
GSM2241712 GS23-Het_prog_5hmC
GSM2241713 GS24-Homo_prog_input
This SubSeries is part of SuperSeries:
GSE84550 Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration
BioProject PRJNA329590
SRA SRP078909

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Supplementary file Size Download File type/resource
GSE84544_RAW.tar 2.2 Gb (http)(custom) TAR (of BEDGRAPH)
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Raw data are available in SRA
Processed data provided as supplementary file

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