Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1256730.fastq.gz | Fastqsanger.gz | |||
| ERR1256740.fastq.gz | Fastqsanger.gz | |||
| ERR1256731.fastq.gz | Fastqsanger.gz | |||
| ERR1256732.fastq.gz | Fastqsanger.gz | |||
| ERR1256733.fastq.gz | Fastqsanger.gz |
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Project description:The tumor suppressor p53 has been studied extensively as a direct transcriptional activator of protein-coding genes. Recent studies, however, have shed light on novel regulatory functions of p53 within noncoding regions of the genome. Here, we use a systematic approach that integrates transcriptome-wide differential expression analysis, genome-wide p53 binding profiles, chromatin state maps, and additional genomic features to characterize the global regulatory roles of p53 in response to DNA damage in both human and mouse fibroblast models. In addition to known p53 targets, we identify many previously unappreciated mRNAs and long noncoding RNAs that are regulated by p53. Moreover, we find that p53 binding events occur predominantly within enhancer elements in both human and mouse systems. The ability to modulate enhancer activity offers an additional layer of complexity to the p53 network and greatly expands the diversity of genomic elements that are directly regulated by p53. Human and Mouse fibroblasts cultured in the presence or absence of doxorubicin followed by RNA-Seq (Human:2 cell lines, each condition in duplicate; Mouse:MEF cell line,each condition in triplicate) and p53 ChIP-Seq (Human:2 cell lines, input and IP for each; Mouse:MEF cell line, input and IP)
2015-04-18 | E-GEOD-55727 | biostudies-arrayexpress
Project description:Cell cycle progression is linked to transcriptome dynamics and variations in the response of pluripotent cells to differentiation cues, through mostly unknown determinants. Here, we characterized the cell cycle–associated transcriptome and proteome of mouse embryonic stem cells (mESCs) in naïve ground state. We found that the thymine DNA glycosylase (TDG) is a cell cycle–regulated co-factor of the tumour suppressor p53. Further, TDG and p53 co-bind ESC-specific cis-regulatory elements and thereby control transcription of p53-dependent genes during self-renewal. We determined that the dynamic expression of TDG is required to promote the cell cycle–associated transcriptional heterogeneity. Moreover, we demonstrated that transient depletion of TDG influences cell fate decisions during the early differentiation of mESCs. Our findings reveal an unanticipated role of TDG in promoting molecular heterogeneity during the cell cycle, and highlight the central role of protein dynamics for the temporal control of cell fate during development.
2023-07-31 | PXD029596 | Pride
Project description:p53 is a critical tumor suppressor and works as a stress-induced transcription factor to induce target genes mediating apoptosis, cell cycle arrest and senescence or other responses. To gain new insights into p53 biology, we used high-throughput sequencing to analyze global p53 transcriptional networks in primary mouse embryo fibroblasts in response to DNA damage. ChIP-sequencing reveals 4785 p53-bound sites in the genome located near 3193 genes involved in diverse biological processes. RNA-sequencing analysis shows that only a subset of p53-bound genes is transcriptionally regulated, yielding a list of 432 p53-bound and regulated genes. Furthermore, we define a list of 1269 basal-p53 regulated genes, of which 253 are p53-bound and basal-p53 regulated. ChIP-seq was performed to determine the genome-wide p53 binding sites in doxorubicin-treated primary MEFs. RNA-seq was used to define differentially expressed genes in response to DNA damage in wild-type and p53-/- MEFs, and basal p53 regulated genes by deriving differentially expressed genes between untreated wild-type and p53-/- MEFs.
2013-04-21 | E-GEOD-46240 | biostudies-arrayexpress
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:RFX7, ANKRA2, and p53-regulated transcriptome in RPE-1
| PRJNA680778 | ENA
Project description:The tumor suppressor p53 plays a crucial role in cellular growth control inducing a plethora of cellular response pathways. The molecular mechanisms that discriminate between the distinct p53-responses towards different stress treatments have remained largely elusive. Here, we have analyzed the p53-regulated pathways induced by two chemotherapeutical treatments, Actinomycin D inducing growth arrest and Etoposide resulting in apoptosis. We found that the genome-wide p53-binding patterns are almost identical upon both treatments notwithstanding transcriptional differences that we observed in genome-wide transcriptome analysis. To assess the role of post-translational modifications in target gene choice and activation we investigated the extent of phosphorylation of Serine 46 of p53 bound to DNA (p53-pS46), a modification that has been linked to apoptosis-pathways, and the extent of phosphorylation of Serine 15 (p53-pS15), a general p53-activation mark. Interestingly, the overall extent of S46 phosphorylation of p53 bound to DNA is considerably higher in cells directed towards apoptosis while the degree of phosphorylation at S15 of DNA bound p53 remains highly similar upon both treatments. Moreover, our data suggest that, following different chemotherapeutical treatments, the extent of chromatin-associated p53 phosphorylated at S46 but not at pS15 is higher on certain apoptosis related target genes, including the BAX and PUMA genes. These data provide evidence that cell fate decisions are not made primarily on the level of general p53 DNA-binding, but possibly through post-translational modifications of chromatin bound p53. ChIP-seq profiles of p53, p53phosphorylated at Serine 15 (p53-pS15) and p53 phosphorylated at Serine 46 (p53-pS46) in U2OS cells treated with either Actinomycin D or Etoposide.
2011-03-24 | E-GEOD-21939 | biostudies-arrayexpress
Project description:Several genome-wide transcriptome analyses that focused on p53-induced cellular responses in many cellular contexts have continued to expand the already vast p53-regulated transcriptional networks. To investigate post-transcriptional controls as an additional dimension of p53-directed gene expression responses we performed translatome analysis by polysomal profiling on MCF7 cells treated with Doxorubicin and Nutlin-3a. A comparison between the transcriptome and the translatome revealed a large number of uncoupled genes, whose transcription changes did not correlate with translation changes. Overall, we establish p53 as a master regulator of translational control and identify many p53 target genes affecting translation that can contribute to p53-dependent cellular responses. Keywords: p53, transcriptome, translatome, polysomal RNA, subpolysomal RNA, uncoupling, Doxorubicin, Nutlin-3a
2014-04-17 | GSE50650 | GEO
Project description:p53 is a critical tumor suppressor and works as a stress-induced transcription factor to induce target genes mediating apoptosis, cell cycle arrest and senescence or other responses. To gain new insights into p53 biology, we used high-throughput sequencing to analyze global p53 transcriptional networks in primary mouse embryo fibroblasts in response to DNA damage. ChIP-sequencing reveals 4785 p53-bound sites in the genome located near 3193 genes involved in diverse biological processes. RNA-sequencing analysis shows that only a subset of p53-bound genes is transcriptionally regulated, yielding a list of 432 p53-bound and regulated genes. Furthermore, we define a list of 1269 basal-p53 regulated genes, of which 253 are p53-bound and basal-p53 regulated.
2013-04-21 | GSE46240 | GEO
Project description:We performed p53 ChIP-seq analysis of Nutlin-treated HCT116 cells to identify high-confident p53 regulated targets. And we performed ChIP-seq using an anti-p53 antibody in HCT116 cells treated with control or iASPP RNAi to identify iASPP regulated p53 targets.
2019-09-23 | GSE113338 | GEO