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| Status |
Public on Nov 15, 2010 |
| Title |
Phosphatidylinositol 3-Kinase (PI3K) Signaling via Glycogen Synthase Kinase-3 (Gsk-3) Regulates DNA Methylation of Imprinted Loci. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2.
Gsk-3 activity serves as a node for several signal transduction pathways, and its regulation of Dnmt3a2 expression raises the possibility that DNA methylation could be transiently affected by different types of environmental stimuli. Our data suggest that modulating Gsk-3 activity could have further reaching effects in the regulation of the epigenome.
Keywords: Gene expression array-based
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| Overall design |
The study was designed to examine the changes in gene expression between wild-type and Gsk-3a-/-;Gsk-3b-/- mouse embryonic stem cells.
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| Contributor(s) |
Popkie AP, Zeidner LC, Albrecht AM, Eckardt S, Newsom DE, Aronow B, Groden J, McLaughlin KJ, White P, Phiel CJ |
| Citation(s) |
21047779 |
| |
| Submission date |
Jan 22, 2010 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Christopher Phiel |
| E-mail(s) |
phiel.1@osu.edu
|
| Organization name |
The Research Institute at Nationwide Children's Hospital
|
| Street address |
700 Children's Drive W432
|
| City |
Columbus |
| State/province |
OH |
| ZIP/Postal code |
43205 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA124089 |
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