|
| Status |
Public on Dec 31, 2015 |
| Title |
Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The Mdm2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that Mdm2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, Mdm2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the Mdm2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. Mdm2 physically associated with EZH2 on chromatin, enhancing the trimethylation of Histone 3 at lysine 27 and the ubiquitination of Histone 2A at lysine 119 (H2AK119) at its target genes. Removing Mdm2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, Mdm2 supports the Polycomb-mediated repression of lineage specific genes independent of p53.
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| |
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| Overall design |
H3K27me3 and H2Ak119ub1 ChIP-Seq
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| |
|
| Contributor(s) |
Wienken M, Dickmanns A, Dobbelstein M |
| Citation missing |
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| |
| Submission date |
Sep 22, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Magdalena Wienken |
| Organization name |
University Medical Center Goettingen
|
| Street address |
Justus-von-Liebig-Weg 11
|
| City |
Goettingen |
| ZIP/Postal code |
37077 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE73602 |
Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner |
|
| Relations |
| BioProject |
PRJNA296550 |
| SRA |
SRP063961 |
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