Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from mouse embryo fibroblast (MEFS)

ABSTRACT: The role of p53 in assuring longevity through prevention of cancer is well established, but how it specifically regulates aging is still controversial. Our assumption is that distinct p53-pathways regulate tumor suppression and aging and that p66Shc is one of the master regulators of the p53 aging function. p66Shc longevity determinant protein acts as a downstream target of p53 and it is indispensable for the ability of activated p53 to induce elevation of intracellular oxidants and apoptosis. We used microarray to gain insight into the mechanism through which p66Shc could regulate p53 oxidative stress dependent activity. Total RNA was extracted from Primary murine embryonic fibroblasts (MEFs) were isolated from 13.5-day-old embryos according to standard procedures from WT, p53KO and p66ShcKO mice. Treatment: Early passage (p.2) MEFs were washed twice with PBS1X solution, and then incubated in DMEM media containing 400 Î¼M of H2O2 or 0.25Î¼g/ml of Doxorubicin (SIGMA) at 37Â°C for four hours.

ORGANISM(S): Mus musculus

SUBMITTER: Simone Minardi

PROVIDER: E-GEOD-28416 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Recently, more than a thousand large intergenic non-coding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediated apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulating their localization to sets of previously active genes. Gene expression profiles of different p53 inducible mouse embryonic fibroblasts (p53LSL/LSL MEFs) across different time points after DNA damage. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 transcriptional response. [1] MEF profiling: p53 LSL/LSL MEFs were treated with adenoCRE for p53 restoration or adenoGFP as control for 24h and treated with 500nM doxorubicin for the indicated times. [2] hnRNPKKD profiling: p53 LSL/LSL MEFs were treated with adenoCRE for p53 restoration for 24h, transfected with siRNA oligos targeting different transcripts for 24h and then treated with 100nM doxorubicin for 13h. [3] lincP21KD profiling: p53 LSL/LSL MEFs were treated with adenoCRE for p53 restoration for 24h, transfected with siRNA oligos targeting different transcripts for 24h and then treated with 100nM doxorubicin for 13h. [4] RAS profiling: For p53 restoration, cultured tumor cell lines were incubated with 500nM 4-hydroxytamoxifen for the indicated times.

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Expression data from mouse embryo fibroblast (MEFS)

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