Genome-wide analysis of tumor suppressive programs during p53-induced regression of Myc-driven lymphomas
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA318256 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3362930.fastq.gz | Fastqsanger.gz | |||
| SRR3362940.fastq.gz | Fastqsanger.gz | |||
| SRR3362950.fastq.gz | Fastqsanger.gz | |||
| SRR3363000.fastq.gz | Fastqsanger.gz | |||
| SRR3363030_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 139 |
Similar Datasets
Project description:The tumor suppressor p53 is a transcription factor that controls the response to stress. Here, we dissected the transcriptional programs triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. p53 recruitment at these sites was mainly mediated through protein-protein or protein-chromatin interactions and, only for a small fraction, through recognition of the 20 base-pair p53 consensus motif. At promoters, p53 binding to the consensus motif was associated with gene induction, but not repression, indicating that the latter was most likely indirect. p53 also targeted unmarked distal sites devoid of activation marks, at which binding was prevalently driven by recognition of the consensus motif. At all sites, our data highlighted a functional role for the canonical, unsplit consensus element, but did not provide evidence for p53 recruitment by split motifs. Altogether, our data highlight key features of genome recognition by p53 and provide unprecedented insight into the pathways associated with p53 re-activation and tumor regression.
2017-02-14 | GSE80193 | GEO
Project description:The tumor suppressor p53 is a transcription factor that controls the response to stress. Here, we dissected the transcriptional programs triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. p53 recruitment at these sites was mainly mediated through protein-protein or protein-chromatin interactions and, only for a small fraction, through recognition of the 20 base-pair p53 consensus motif. At promoters, p53 binding to the consensus motif was associated with gene induction, but not repression, indicating that the latter was most likely indirect. p53 also targeted unmarked distal sites devoid of activation marks, at which binding was prevalently driven by recognition of the consensus motif. At all sites, our data highlighted a functional role for the canonical, unsplit consensus element, but did not provide evidence for p53 recruitment by split motifs. Altogether, our data highlight key features of genome recognition by p53 and provide unprecedented insight into the pathways associated with p53 re-activation and tumor regression.
2017-02-14 | GSE80186 | GEO
Project description:The tumor suppressor p53 is a transcription factor that controls the response to stress. Here, we dissected the transcriptional programs triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. p53 recruitment at these sites was mainly mediated through protein-protein or protein-chromatin interactions and, only for a small fraction, through recognition of the 20 base-pair p53 consensus motif. At promoters, p53 binding to the consensus motif was associated with gene induction, but not repression, indicating that the latter was most likely indirect. p53 also targeted unmarked distal sites devoid of activation marks, at which binding was prevalently driven by recognition of the consensus motif. At all sites, our data highlighted a functional role for the canonical, unsplit consensus element, but did not provide evidence for p53 recruitment by split motifs. Altogether, our data highlight key features of genome recognition by p53 and provide unprecedented insight into the pathways associated with p53 re-activation and tumor regression.
2017-02-14 | GSE80187 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-02-14 | GSE80195 | GEO
Project description:c-myc-3'RR mice prone to develop Burkitt lymphoma (BL) were crossed with p53+/- mice in order to obtain c-myc-3'RR/p53+/- mice. These mice develop a wider spectrum of lymphoma including BL, mantle cell lymphoma (MCL) and plasma cell lymphoma (PCL). Transcriptoma analysis of these lymphomas is investigated in these arrays.
2012-01-05 | GSE31814 | GEO
Project description:c-myc-3'RR mice prone to develop Burkitt lymphoma (BL) were crossed with p53+/- mice in order to obtain c-myc-3'RR/p53+/- mice. These mice develop a wider spectrum of lymphoma including BL, mantle cell lymphoma (MCL) and plasma cell lymphoma (PCL). Transcriptoma analysis of these lymphomas is investigated in these arrays. Four different plasma cell lymphoma (PCL1-4), three different mantle cell lymphoma (MCL1-4) and four different Burkitt lymphoma (BL1-4) were compared.
2012-01-05 | E-GEOD-31814 | biostudies-arrayexpress
Project description:For the most frequently inactivated tumor suppressor p53, genetic mouse models have demonstrated regression of p53-null tumors upon p53 reactivation. While this was shown in tumor models driven by p53 loss as the initiating lesion, many tumors initially develop in the presence of wild-type p53, acquire aberrations in the p53 pathway to bypass p53-mediated tumor suppression, and inactivate p53 itself only at later stages during metastatic progression or therapy. To explore the efficacy of p53 reactivation in this scenario, we used a reversibly switchable p53 (p53ERTAM) mouse allele to generate Eµ-Myc-driven lymphomas in the presence of active p53 and, after full lymphoma establishment, switched off p53 to model late-stage p53 inactivation.
2019-10-18 | E-MTAB-8015 | biostudies-arrayexpress
Project description:Myc and p53 proteins are closely associated with many physiological cellular functions, including immune response and lymphocyte survival, and are expressed in the lymphoid organs, which are sites for the development and activation of B-cell malignancies. Genetic alterations and other mechanisms resulting in constitutive activation, rearrangement, or mutation of MYC and TP53 contribute to the development of lymphomas, progression and therapy resistance by gene dysregulation, activation of downstream anti-apoptotic pathways, and unfavorable microenvironment interactions. The cross-talk between the Myc and p53 proteins contributes to the inferior prognosis in many types of B-cell lymphomas. In this review, we present the physiological roles of Myc and p53 proteins, and recent advances in understanding the pathological roles of Myc, p53, and their cross-talk in lymphoid neoplasms. In addition, we highlight clinical trials of novel agents that directly or indirectly inhibit Myc and/or p53 protein functions and their signaling pathways. Although, to date, these trials have failed to overcome drug resistance, the new results have highlighted the clinical efficiency of targeting diverse mechanisms of action with the goal of optimizing novel therapeutic opportunities to eradicate lymphoma cells.
| S-EPMC6926120 | biostudies-literature
Project description:The suppression of oncogenic levels of MYC is sufficient to induce sustained tumor regression associated with proliferative arrest, differentiation, cellular senescence and/or apoptosis, a phenomenon known as oncogene addiction. However, after prolonged inactivation of MYC in a conditional transgenic mouse model of Em-tTA/tetO-MYC T-acute lymphomablastic lymphoma (T-ALL), some of the tumors recur, recapitulating what is frequently observed in human tumors in response to targeted therapies. Here we report that these recurring lymphomas express high levels of either transgenic or endogenous Myc suggesting that tumors continue to be addicted to oncogenic levels of MYC. Many of the recurring lymphomas (76%) harbored mutations in the tetracycline transactivator (tTA) resulting in expression of the MYC transgene even in the presence of doxycycline. Many of the remaining recurring tumors expressed high levels of endogenous Myc which was in some cases associated with a genomic rearrangement of the endogenous Myc locus or overexpression of Notch1. Gene expression profiling confirmed that the primary and recurring tumors have highly similar transcriptomes. Importantly, shRNA-mediated suppression of the high levels of MYC in recurring tumors elicited both suppression of proliferation and increased apoptosis confirming that these tumors remain oncogene addicted. These results suggest that tumors caused by MYC overexpression remain addicted to high levels of expression of this oncogene. 13 samples, no replicates included
2011-09-23 | E-GEOD-32341 | biostudies-arrayexpress
Project description:Genome-wide analysis of tumor suppressive programs during p53-induced regression of Myc-driven lymphomas [DNaseI-seq]
| PRJNA318257 | ENA