The p53 transcriptional response across tumor types reveals core and outcome-specific signatures modulated by cis-regulatory lncRNAs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE163404 | GEO | 2021/07/13
REPOSITORIES: GEO
Similar Datasets
Project description:The p53 pathway is a universal tumor suppressor mechanism but the differences of the p53 transcriptional response to oncogenic stress across different tumor types are poorly understood. Using a panel of murine cancer cell lines, we observed that the majority of p53-bound sites were tumor type-specific. Analysis of common p53 targets defined a small but robust core signature and revealed a senescence-specific repression geneset. Characterization of novel transcripts identified p53-induced lncRNAs, which frequently associated with chromatin and regulated their neighboring mRNAs. These findings shed light on the unique and shared p53 transcriptional signatures across different contexts and clarify the contributions of lncRNAs to the p53 transcriptome.
2021-07-13 | GSE163403 | GEO
Project description:The p53 pathway is a universal tumor suppressor mechanism but the differences of the p53 transcriptional response to oncogenic stress across different tumor types are poorly understood. Using a panel of murine cancer cell lines, we observed that the majority of p53-bound sites were tumor type-specific. Analysis of common p53 targets defined a small but robust core signature and revealed a senescence-specific repression geneset. Characterization of novel transcripts identified p53-induced lncRNAs, which frequently associated with chromatin and regulated their neighboring mRNAs. These findings shed light on the unique and shared p53 transcriptional signatures across different contexts and clarify the contributions of lncRNAs to the p53 transcriptome.
2021-07-13 | GSE163402 | GEO
Project description:The p53 transcriptional response across tumor types reveals core and outcome-specific signatures modulated by cis-regulatory lncRNAs
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Project description:The p53 transcriptional response across tumor types reveals core and outcome-specific signatures modulated by cis-regulatory lncRNAs [ChIP-seq]
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Project description:The p53 transcriptional response across tumor types reveals core and outcome-specific signatures modulated by cis-regulatory lncRNAs [RNA-seq]
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Project description:The p53 pathway is a universal tumor suppressor mechanism that limits tumor progression by triggering apoptosis or permanent cell cycle arrest, called senescence. In recent years, efforts to reactivate p53 function in cancer have proven to be a successful therapeutic strategy in murine models and have gained traction with the development of a range of small molecules targeting mutant p53. However, knowledge of the downstream mediators of p53 reactivation in different oncogenic contexts has been limited. Here, we utilized a panel of murine cancer cell lines from three distinct tumor types susceptible to alternative outcomes following p53 restoration to define unique and shared p53 transcriptional signatures. While we found that the majority of p53-bound sites and p53-responsive transcripts are tumor-type specific, analysis of shared targets identified a core signature of genes activated by p53 across all contexts. Furthermore, we identified repression of E2F and Myc target genes as a key feature of senescence. Characterization of p53-induced transcripts revealed core and senescence-specific long noncoding RNAs (lncRNAs) that are predominantly chromatin associated and whose production is coupled to cis-regulatory activities. Functional investigation of the contributions of p53-induced lncRNAs to p53-dependent outcomes highlighted Pvt1b, the p53-dependent isoform of Pvt1, as a mediator of p53-dependent senescence via Myc repression. Inhibition of Pvt1b led to decreased activation of senescence markers and increased levels of markers of proliferation. These findings shed light on the core and outcome-specific p53 restoration signatures across different oncogenic contexts and underscore the key role of the p53-Pvt1b-Myc regulatory axis in mediating proliferative arrest.
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