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Status |
Public on Jul 01, 2013 |
Title |
Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells (Affymetrix) |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
The effects of diverse stresses on promoter selectivity and transcription regulation by the tumor suppressor p53 are poorly understood. We have taken a comprehensive approach to characterizing the human p53 network that includes p53 levels, binding, expression and chromatin changes under diverse stresses. Human osteosarcoma U2OS cells treated with anti-cancer drugs Doxorubicin or Nutlin-3 led to strikingly different p53 gene binding patterns based on ChIP-seq experiments. While two contiguous RRRCWWGYYY decamers is the consensus binding motif, p53 can bind a single decamer and function in vivo. Although the number of sites bound by p53 was 6-times greater for Nutlin-3 than Doxorubicin, expression changes induced by Nutlin-3 were much less dramatic compared to Doxorubicin. Unexpectedly, the solvent DMSO alone induced p53 binding to many sites common to Doxorubicin; however, this binding had no effect on target gene expression. Together, these data imply a two-stage mechanism for p53 transactivation where p53 binding only constitutes the first stage. Furthermore, both p53 binding and transactivation were associated with increased active histone modification H3K4me3. We discovered 149 putative new p53 target genes including several that are relevant to tumor suppression, revealing potential new targets for cancer therapy and expanding our understanding of the p53 regulatory network.
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Overall design |
Gene expression analysis (using Affymetrix Human Genome U133 Plus 2.0 GeneChip® arrays) of the p53 response in U2OS cells treated with either Doxorubicin or Nutlin-3, relative to their controls No Treatment and DMSO, respectively.
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Contributor(s) |
Menendez D, Nguyen TT, Freudenberg JM, Mathew VJ, Anderson CW, Jothi R, Resnick MA |
Citation(s) |
23775793 |
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Submission date |
Apr 30, 2013 |
Last update date |
Mar 25, 2019 |
Contact name |
NIEHS Microarray Core |
E-mail(s) |
microarray@niehs.nih.gov, liuliw@niehs.nih.gov
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Organization name |
NIEHS
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Department |
DIR
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Lab |
Microarray Core
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Street address |
111 T.W. Alexander Drive
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City |
RTP |
State/province |
NC |
ZIP/Postal code |
27709 |
Country |
USA |
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Platforms (1) |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (12)
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This SubSeries is part of SuperSeries: |
GSE46642 |
Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells |
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Relations |
BioProject |
PRJNA200647 |
Supplementary file |
Size |
Download |
File type/resource |
GSE46493_RAW.tar |
64.7 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
Processed data included within Sample table |
Processed data provided as supplementary file |
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