Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo [DNAse-Seq]

ABSTRACT: The tumor suppressor p53 is a transcription factor that coordinates the cellular response to DNA damage. Here we provide an integrated analysis of p53 genomic occupancy and p53-dependent gene regulation in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation, providing insight into general principles of p53 activity in vivo. In unstressed conditions, p53 bound few genomic targets; induction of p53 by ionizing radiation increased the number of p53 bound sites, leading to highly overlapping profiles in the different cell types. Comparison of these profiles with chromatin features in unstressed B cells revealed that, upon activation, p53 localized at active promoters, distal enhancers, and a smaller set of unmarked distal regions. At promoters, recognition of the canonical p53 motif as well as binding strength were associated with p53-dependent transcriptional activation, but not repression, indicating that the latter was most likely indirect. p53-activated targets constituted the core of a cell type-independent response, superimposed onto a cell type-specific program. Core response genes included most of the known p53-regulated genes, as well as many new ones. Our data represent a unique characterization of the p53-regulated response to ionizing radiation in vivo.

ORGANISM(S): Mus musculus

PROVIDER: GSE71177 | GEO | 2015/08/24

SECONDARY ACCESSION(S): PRJNA290506

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo [ChIP-Seq]

Project description:The tumor suppressor p53 is a transcription factor that coordinates the cellular response to DNA damage. Here we provide an integrated analysis of p53 genomic occupancy and p53-dependent gene regulation in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation, providing insight into general principles of p53 activity in vivo. In unstressed conditions, p53 bound few genomic targets; induction of p53 by ionizing radiation increased the number of p53 bound sites, leading to highly overlapping profiles in the different cell types. Comparison of these profiles with chromatin features in unstressed B cells revealed that, upon activation, p53 localized at active promoters, distal enhancers, and a smaller set of unmarked distal regions. At promoters, recognition of the canonical p53 motif as well as binding strength were associated with p53-dependent transcriptional activation, but not repression, indicating that the latter was most likely indirect. p53-activated targets constituted the core of a cell type-independent response, superimposed onto a cell type-specific program. Core response genes included most of the known p53-regulated genes, as well as many new ones. Our data represent a unique characterization of the p53-regulated response to ionizing radiation in vivo. Mapping p53 binding sites in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation

2015-08-24 | E-GEOD-71175 | biostudies-arrayexpress

Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo [DNAse-Seq]

2015-08-24 | E-GEOD-71177 | biostudies-arrayexpress

Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo [RNA-Seq]

Project description:The tumor suppressor p53 is a transcription factor that coordinates the cellular response to DNA damage. Here we provide an integrated analysis of p53 genomic occupancy and p53-dependent gene regulation in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation, providing insight into general principles of p53 activity in vivo. In unstressed conditions, p53 bound few genomic targets; induction of p53 by ionizing radiation increased the number of p53 bound sites, leading to highly overlapping profiles in the different cell types. Comparison of these profiles with chromatin features in unstressed B cells revealed that, upon activation, p53 localized at active promoters, distal enhancers, and a smaller set of unmarked distal regions. At promoters, recognition of the canonical p53 motif as well as binding strength were associated with p53-dependent transcriptional activation, but not repression, indicating that the latter was most likely indirect. p53-activated targets constituted the core of a cell type-independent response, superimposed onto a cell type-specific program. Core response genes included most of the known p53-regulated genes, as well as many new ones. Our data represent a unique characterization of the p53-regulated response to ionizing radiation in vivo. Total RNA profiling of gene expression in the splenic B and non-B cell compartments of wild-type and Trp53-/-mice exposed to whole-body ionizing radiation by Illumina sequencing

2015-08-24 | E-GEOD-71176 | biostudies-arrayexpress

Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo [ChIP-Seq]

2015-08-24 | GSE71175 | GEO

Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo [RNA-Seq]

2015-08-24 | GSE71176 | GEO

Sensors, Pathways and Transcription factors regulating IR-induced inflammatory transcriptional output [ChIP-seq]

Project description:Radiation induced interferon response is mediated by IRF1 but not by the IRF3. Phosphorylated p53 binds strongly within 1kb of TTS of p53 dependent genes that are potently induced by ionizing radiation.

2017-10-01 | GSE100962 | GEO

Ma2005-digital response of p53 to DNA damage-ATM Activation Module

Project description:Recent observations show that the single-cell response of p53 to ionizing radiation (IR) is “digital” in that it is the number of oscillations rather than the amplitude of p53 that shows dependence on the radiation dose. We present a model of this phenomenon. In our model, double-strand break (DSB) sites induced by IR interact with a limiting pool of DNA repair proteins, forming DSB–protein complexes at DNA damage foci. The persisting complexes are sensed by ataxia telangiectasia mutated (ATM), a protein kinase that activates p53 once it is phosphorylated by DNA damage. The ATM-sensing module switches on or off the downstream p53 oscillator, consisting of a feedback loop formed by p53 and its negative regulator, Mdm2. In agreement with experiments, our simulations show that by assuming stochasticity in the initial number of DSBs and the DNA repair process, p53 and Mdm2 exhibit a coordinated oscillatory dynamics upon IR stimulation in single cells, with a stochastic number of oscillations whose mean increases with IR dose. The damped oscillations previously observed in cell populations can be explained as the aggregate behavior of single cell

2020-05-13 | MODEL2005130001 | BioModels

Quiescent keratinocytes and fibroblasts: radiation dose response

Project description:Skin is usually exposed during human exposures to ionizing radiation, however there are few experiments that evaluate the radiation responsiveness of the cells of the epidermis (keratinocytes) and those of the dermis (fibroblasts) in the same studies. We evaluated the transcriptional responses of quiesent primary keratinocytes and fibroblasts from the same individual and compared them with quiescent keratinocytes and fibroblasts that were immortalized by human telomerase (hTert). The primary transcriptional responses to 10-500 cGy ionizing radiation were p53-mediated responses; however, we did identify distinct responses between the keratinocytes and the fibroblasts. Keywords: keratinocytes and fibroblasts - dose response to ionizing radiation

2009-05-31 | GSE14466 | GEO

Genome-wide analysis of tumor suppressive programs during p53-induced regression of Myc-driven lymphomas [DNaseI-seq]

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

Genome-wide analysis of tumor suppressive programs during p53-induced regression of Myc-driven lymphomas [RNA-Seq]

2017-02-14 | GSE80187 | GEO