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Status |
Public on Jan 19, 2010 |
Title |
p53 binding in mouse embryonic stem cells untreated or treated with adriamycin |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by array
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Summary |
Both p53 and the Wnt signaling pathways play important roles in tumorigenesis and development. However, few studies, particularly on a genome-wide scale, have linked these two pathways. Here we show that p53 directly regulates the Wnt signaling pathway in murine embryonic stem cells (mESCs) using an integrated genome-wide approach. A chromatin-immunoprecipitation-based microarray assay (ChIP-chip) reveals that the Wnt signaling pathway is significantly over-represented in p53 bound genes. Using gene expression microarray and real-time PCR, we demonstrate that the expressions of many Wnts are robustly induced by various stresses, including DNA damage and hypoxia that activate p53. Importantly, the activation of p53 is a prerequisite for the induction of Wnts. Moreover, conditional medium (CM) collected from ultraviolet (UV)-treated mESCs contains an anti-differentiation activity, which can be lowered by either the addition of Wnt signaling inhibitors into the CM or the reduction of p53 levels in UV-treated mESCs. These results suggest that stressed mESCs utilize the p53-Wnt signaling axis to signal neighboring mESCs to delay the differentiation. Together, our results uncover a novel connection between p53 and the Wnt signaling pathways in mediating cell-to-cell communication in mESCs, and provide insights into the functions of these two pathways in tumorigenesis and development
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Overall design |
ChIP-chip assay was done per Agilent’s ChIP-chip protocol (Version 10.0). The goal of this experiment is to identify the p53 binding sites in cells untreated or treated with adriamycin (DNA damage).
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Contributor(s) |
Mangmang L, Kyoung-Hwa L, Aleksandra M, Xinyue Z, Hongling L, Lingyi C, Xiaolin W, Jing H |
Citation(s) |
20018659 |
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Submission date |
Jun 04, 2009 |
Last update date |
Dec 06, 2012 |
Contact name |
Jing Huang |
E-mail(s) |
[email protected]
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Organization name |
National Cancer Institute
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Lab |
Cancer Biology and Genetics
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Street address |
37 Convent Dr. 37/3140
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
MD 20892 |
Country |
USA |
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Platforms (2) |
GPL4128 |
Agilent-014716 Mouse Promoter ChIP-on-Chip Set 244K, Microarray 1 of 2 (G4490A) (Feature Number version) |
GPL4129 |
Agilent-014717 Mouse Promoter ChIP-on-Chip Set 244K, Microarray 2 of 2 (G4490A) (Feature Number version) |
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Samples (4)
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GSM412770 |
1st design mouse embryonic stem cells untreated |
GSM412771 |
1st design mouse embryonic stem cells adriamycin-treated |
GSM412773 |
2nd design mouse embryonic stem cells untreated |
GSM412774 |
2nd design mouse embryonic stem cells adriamycin-treated |
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Relations |
BioProject |
PRJNA116373 |