ATAC-Seq on DNA damaged human fibroblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE76417 | GEO | 2016/09/26
SECONDARY ACCESSION(S): PRJNA307255
REPOSITORIES: GEO
Similar Datasets
Project description:Long noncoding RNAs (lncRNAs) are prevalent genes with frequently exquisite regulation but mostly unknown functions. Here we demonstrate a role of lncRNAs in guiding signal transduction. DNA damage activates transcription of DINO (Damage Induced NOncoding) via p53. DINO knockdown blocks DNA damage-induced gene expression and cell cycle arrest. Conversely, enforced expression of DINO activates damage signaling without DNA damage. DINO binds p53 and selectively promotes SET7 methylation of p53 at lysine 372 over other substrates, which stabilizes p53 in an auto-amplification loop. Our results suggest that inducible lncRNA can achieve catalysis-like effects to rewire cellular signaling networks. RNA was isolated from human fetal lung fibroblasts, HCT116 p53+/+, or HCT116 p53-/- cells treated with doxorubicin or sham for 26 hours. Human fetal lung fibroblasts were transfected with siRNAs targeting DINO or non-targeting control and subsequently treated with doxorubicin for 26 hours.
2012-11-20 | E-GEOD-42368 | biostudies-arrayexpress
Project description:Long noncoding RNAs (lncRNAs) are prevalent genes with frequently exquisite regulation but mostly unknown functions. Here we demonstrate a role of lncRNAs in guiding signal transduction. DNA damage activates transcription of DINO (Damage Induced NOncoding) via p53. DINO knockdown blocks DNA damage-induced gene expression and cell cycle arrest. Conversely, enforced expression of DINO activates damage signaling without DNA damage. DINO binds p53 and selectively promotes SET7 methylation of p53 at lysine 372 over other substrates, which stabilizes p53 in an auto-amplification loop. Our results suggest that inducible lncRNA can achieve catalysis-like effects to rewire cellular signaling networks.
2012-11-20 | GSE42368 | GEO
Project description:Examine the chormatin localization of DINO in DNA damaged human U2OS cells using DINO ChIRP-seq.
2016-09-26 | GSE76418 | GEO
Project description:LncRNA DINO guides DNA damage signaling
| PRJNA307252 | ENA
Project description:After DNA damage, cells activate p53, a tumor suppressor gene, and select a cell fate (e.g., DNA repair, cell cycle arrest, or apoptosis). Recently, a p53 oscillatory behavior was observed following DNA damage. However, the relationship between this p53 oscillation and cell-fate selection is unclear. Here, we present a novel model of the DNA damage signaling pathway that includes p53 and whole cell cycle regulation and explore the relationship between p53 oscillation and cell fate selection. The simulation run without DNA damage qualitatively realized experimentally observed data from several cell cycle regulators, indicating that our model was biologically appropriate. Moreover, the comprehensive sensitivity analysis for the proposed model was implemented by changing the values of all kinetic parameters, which revealed that the cell cycle regulation system based on the proposed model has robustness on a fluctuation of reaction rate in each process. Simulations run with four different intensities of DNA damage, i.e. Low-damage, Medium-damage, High-damage, and Excess-damage, realized cell cycle arrest in all cases. Low-damage, Medium-damage, High-damage, and Excess-damage corresponded to the DNA damage caused by 100, 200, 400, and 800 J/m(2) doses of UV-irradiation, respectively, based on expression of p21, which plays a crucial role in cell cycle arrest. In simulations run with High-damage and Excess-damage, the length of the cell cycle arrest was shortened despite the severe DNA damage, and p53 began to oscillate. Cells initiated apoptosis and were killed at 400 and 800 J/m(2) doses of UV-irradiation, corresponding to High-damage and Excess-damage, respectively. Therefore, our model indicated that the oscillatory mode of p53 profoundly affects cell fate selection.
2020-04-27 | BIOMD0000000939 | BioModels
Project description:Integrated-systems model of oxidative stress connecting NRF2 and p53 signaling pathways. Additional crosstalk linking oxidative stress to p53 inhibition, p53 to NRF2 through p21, and NRF2 to MDM2 was incorporated in this model. The NRF2 pathway was encoded as first- and second-order rate equations for KEAP1 oxidation and NRF2 stabilization; NRF2-mediated transcription of antioxidant enzymes was modeled as a Hill function. The p53 pathway was reconstructed from a delay differential equation model of p53 signaling in response to DNA damage. To adapt the p53 DNA-damage model to respond to oxidative stress, we used a first-order oxidation reaction of ATM/CHEK2 by intracellular H2O2.
The integrated base model of NRF2–p53 oxidative-stress signaling contains 42 reactions and 22 ordinary differential equations (ODEs).
2021-10-29 | MODEL2110270001 | BioModels
Project description:NFBD1 (nuclear factor with BRCT domains 1), also known as MDC1 (mediator of DNA damage signaling 1), is a protein involved in the ATM signaling pathway in response to DNA damage. In addition to a role in signaling, NFBD1 possesses transactivation activity, suggesting that it may influence transcription. Furthermore, NFBD1 affects p53-mediated transcription in the presence of the DNA damaging agent adriamycin. Our goal was to determine if NFBD1 affects global gene expression with or without ionizing radiation-induced DNA damage. Moreover, we sought to separate p53-dependent from p53-independent events. Illumina microarray analysis was carried out on RNA extracted from cells treated with and without NFBD1 shRNA and/or p53 shRNA in the presence and absence of DNA damage. Surprisingly, we found that the expression of NFBD1-regulated genes was changed in both the presence and absence of DNA damage. Furthermore, most NFBD1-regulated genes were regulated independently of p53. The identification of NFBD1-regulated genes was confirmed with a second NFBD1-directed shRNA sequence. The role of NFBD1 in global gene expression both in the presence and absence of ionizing radiation was determined. p53-dependent and p53-dependent events regulated by NFBD1 depletion were studied. U2OS cells were treated with control, NFBD1 shRNA, and/or p53 shRNA-expressing retrovirus. Cells were then treated with ionizing radiation and total RNA was isolated for Illumina microarray analysis.
2011-06-16 | E-GEOD-23010 | biostudies-arrayexpress
Project description:This is the model described the article:
GSK3 and p53 - is there a link in Alzheimer's disease?
Carole J Proctor and Douglas A Gray Molecular Neurodegeneration
2010, 5:7;
doi: 10.1186/1750-1326-5-7
Abstract:
Background:
Recent evidence suggests that glycogen synthase kinase-3beta (GSK3beta) is implicated in both sporadic and familial forms of Alzheimer's disease. The transcription factor, p53 also plays a role and has been linked to an increase in tau hyperphosphorylation although the effect is indirect. There is also evidence that GSK3beta and p53 interact and that the activity of both proteins is increased as a result of this interaction. Under normal cellular conditions, p53 is kept at low levels by Mdm2 but when cells are stressed, p53 is stabilised and may then interact with GSK3beta. We propose that this interaction has an important contribution to cellular outcomes and to test this hypothesis we developed a stochastic simulation model.
Results:
The model predicts that high levels of DNA damage leads to increased activity of p53 and GSK3beta and low levels of aggregation but if DNA damage is repaired, the aggregates are eventually cleared. The model also shows that over long periods of time, aggregates may start to form due to stochastic events leading to increased levels of ROS and damaged DNA. This is followed by increased activity of p53 and GSK3beta and a vicious cycle ensues.
Conclusions:
Since p53 and GSK3beta are both involved in the apoptotic pathway, and GSK3beta overactivity leads to increased levels of plaques and tangles, our model might explain the link between protein aggregation and neuronal loss in neurodegeneration.
Notes:
The original model submitted by the author had events in it. Since, this model is intended for Stochastic Simulation run and Copasi cannot handle events in Stochastic run, I have replaced the events with piecewise assignment rule. -Viji
This model is an extension of Proctor_p53_Mdm2_ATM ( BIOMD0000000188
).
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team.
For more information see the terms of use
.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2010-01-27 | BIOMD0000000286 | BioModels
Project description:PATZ1 is a DNA damage responsive transcription factor that inhibits p53 function
| PRJNA275243 | ENA
Project description:Deregulated expression of the c-MYC oncogene induces unscheduled DNA replication, DNA damage, and activation of the p53 tumor suppressor. The AP4 transcription factor is a direct c-MYC target gene involved in cell proliferation, epithelial-mesenchymal transition, and stemness, as well as suppression of DNA damage and senescence. Here, we analyzed the role of AP4 and p53 downstream of c-MYC activation using a CRISPR/Cas9-approach in MCF-7 cells.
2023-03-01 | GSE221265 | GEO