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Insights into p53 transcriptional function via genome-wide chromatin occupancy and gene expression analysis
Open accessAbstract
The tumor-suppressor p53 can induce various biological responses. Yet, it is not clear whether it is p53 in vivo promoter selectivity that triggers different transcription programs leading to different outcomes. Our analysis of genome-wide chromatin occupancy by p53 using chromatin immunoprecipitation (ChIP)-seq revealed 'p53 default program', that is, the pattern of major p53-bound sites that is similar upon p53 activation by nutlin3a, reactivation of p53 and induction of tumor cell apoptosis (RITA) or 5-fluorouracil in breast cancer cells, despite different biological outcomes. Parallel analysis of gene expression allowed identification of 280 novel p53 target genes, including p53-repressed AURKA. We identified Sp1 as one of the p53 modulators, which confer specificity to p53-mediated transcriptional response upon RITA. Further, we found that STAT3 antagonizes p53-mediated repression of a subset of genes, including AURKA.
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The multiple mechanisms that regulate p53 activity and cell fate
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iRegulon: From a Gene List to a Gene Regulatory Network Using Large Motif and Track Collections
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“When extending the analysis and including target genes recently reported in literature [58,59,68], it becomes clear that most overlap coincides within this metatargetome (34/44) (Table S6).”
BackgroundProteogenomic Characterization of Endometrial Carcinoma
Dou, Y., Kawaler, E. A., Cui Zhou, D., Gritsenko, M. A., Huang, C., Blumenberg, L., Karpova, A., Petyuk, V. A., Savage, S. R., Satpathy, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.01.026 · Cited by 485
“The mutationtype-specific effects described above appear to be unique to EC; we examined the CPTAC data for ovarian and colon cancer, where TP53 mutations are very common, but observed no change in AURKA, CDK1, XPO1, or STK11 protein levels associated with the type of TP53 mutation (Figure S3H).”
BackgroundInfluentialSelf-citationKenzelmann Broz, D., Spano Mello, S., Bieging, K. T., Jiang, D., Dusek, R. L., Brady, C. A., Sidow, A., & Attardi, L. D. (2013) · Genes & Development · doi:10.1101/gad.212282.112 · Cited by 443
Metadata
- Authors
- Nikulenkov, F., Spinnler, C., Li, H., Tonelli, C., Shi, Y., Turunen, M., Kivioja, T., Ignatiev, I., Kel, A., Taipale, J., & Selivanova, G.
- Venue
- Cell Death & Differentiation
- Published
- 2012-07-13
- Volume
- 19
- Issue
- 12
- Pages
- 1992-2002
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W1982718063
- Cited by
- 181
- References
- 10
- FWCI
- 11.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
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