P53 binding and gene expression profiles in Drosophila postmitotic and embryonic tissue
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA430366 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6497501_1.fastq.gz | Fastqsanger.gz | |||
| SRR6497501_2.fastq.gz | Fastqsanger.gz | |||
| SRR6497502_1.fastq.gz | Fastqsanger.gz | |||
| SRR6497502_2.fastq.gz | Fastqsanger.gz | |||
| SRR6497503_1.fastq.gz | Fastqsanger.gz |
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Project description:TP53 is the most frequently mutated gene in human cancers, and despite intensive research efforts, genome-scale studies of p53 function in whole animal models are rare. Yet the need for such in vivo studies is underscored by recent challenges to established models indicating that unappreciated p53 functions contribute to tumor suppression. Here we leveraged the Drosophila system to interrogate p53 function in a postmitotic context. In the developing fly, p53 robustly activates important apoptotic genes in response to radiation-induced DNA damage. We have recently shown that a p53 enhancer near the cell death gene reaper (p53RErpr), forms chromatin contacts and enables p53 target activation through long genomic distances. Interestingly, we found that this canonical p53 apoptotic program fails to activate in response to radiation in postmitotic tissue. Furthermore, the lack of apoptotic responses was not associated with altered chromatin contacts; instead we determined that p53 does not occupy the p53RErpr enhancer in postmitotic tissue. In addition, we conducted RNA-seq and ChIP-seq studies to directly compare the developing and postmitotic tissues, and we determined that p53 regulates distinct transcriptional programs in adult heads, which include DNA repair, metabolism and proteolysis genes. Strikingly, in the postmitotic context p53 binding landscapes were poorly correlated with nearby transcriptional effects, raising the possibility that p53 enhancers could be generally acting through long distances.
2019-07-15 | GSE109292 | GEO
Project description:DNA damage has been implicated in neurodegenerative disorders, including Alzheimer’s disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, synaptic function, in p53-mediated neuroprotection. We then demonstrate that the control of synaptic genes by p53 is conserved in mammals. Collectively, our results implicate synaptic function as a central target in p53-dependent protection from neurodegeneration. 4 samples: tau vs. control
2015-01-06 | E-GEOD-40418 | biostudies-arrayexpress
Project description:DNA damage has been implicated in neurodegenerative disorders, including Alzheimer’s disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, synaptic function, in p53-mediated neuroprotection. We then demonstrate that the control of synaptic genes by p53 is conserved in mammals. Collectively, our results implicate synaptic function as a central target in p53-dependent protection from neurodegeneration.
2015-01-06 | GSE40418 | GEO
Project description:The goal is to profile p53 binding sites in Nutlin-treated mouse embryonic stem cells.
2021-01-31 | GSE63666 | GEO
Project description:TP53 is the most frequently mutated gene in human cancers, and despite intensive research efforts, genome-scale studies of p53 function in whole animal models are rare. The need for such in vivo studies is underscored by recent challenges to established paradigms, indicating that unappreciated p53 functions contribute to cancer prevention. Here we leveraged the Drosophila system to interrogate p53 function in a postmitotic context. In the developing embryo, p53 robustly activates important apoptotic genes in response to radiation-induced DNA damage. We recently showed that a p53 enhancer (p53RErpr) near the cell death gene reaper forms chromatin contacts and enables p53 target activation across long genomic distances. Interestingly, we found that this canonical p53 apoptotic program fails to activate in adult heads. Moreover, this failure to exhibit apoptotic responses was not associated with altered chromatin contacts. Instead, we determined that p53 does not occupy the p53RErpr enhancer in this postmitotic tissue as it does in embryos. Through comparative RNA-seq and chromatin immunoprecipitation-seq studies of developing and postmitotic tissues, we further determined that p53 regulates distinct transcriptional programs in adult heads, including DNA repair, metabolism, and proteolysis genes. Strikingly, in the postmitotic context, p53-binding landscapes were poorly correlated with nearby transcriptional effects, raising the possibility that p53 enhancers could be generally acting through long distances.
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Project description:This study describes the binding profile of WDR5, p53 and H3K4Me3 in mouse embryonic bodies at day 2 (WT, Wdr5 KO, Wdr5 and p53 double knockout)
2019-11-25 | GSE140899 | GEO
Project description:Both p53 and the Wnt signaling pathways play important roles in tumorigenesis and development. However, few studies, particularly on a genome-wide scale, have linked these two pathways. Here we show that p53 directly regulates the Wnt signaling pathway in murine embryonic stem cells (mESCs) using an integrated genome-wide approach. A chromatin-immunoprecipitation-based microarray assay (ChIP-chip) reveals that the Wnt signaling pathway is significantly over-represented in p53 bound genes. Using gene expression microarray and real-time PCR, we demonstrate that the expressions of many Wnts are robustly induced by various stresses, including DNA damage and hypoxia that activate p53. Importantly, the activation of p53 is a prerequisite for the induction of Wnts. Moreover, conditional medium (CM) collected from ultraviolet (UV)-treated mESCs contains an anti-differentiation activity, which can be lowered by either the addition of Wnt signaling inhibitors into the CM or the reduction of p53 levels in UV-treated mESCs. These results suggest that stressed mESCs utilize the p53-Wnt signaling axis to signal neighboring mESCs to delay the differentiation. Together, our results uncover a novel connection between p53 and the Wnt signaling pathways in mediating cell-to-cell communication in mESCs, and provide insights into the functions of these two pathways in tumorigenesis and development
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Project description:Purpose: We investigated the molecular function of the nuclear protein, Akirin2 (Aki2), in postmitotic excitatory cortical neurons and neural progenitor cells of the embryonic dorsal telencephalon. Method: We performed total RNA-Sequencing on the cortex of P35 CaMK-Cre;Aki2fl/fl mice and age matched controls. We compared this transcriptomic database to one obtained through total RNA-Sequencing of E10.5 Emx1-Cre;Aki2fl/fl dorsal telencephalon and age-matched controls . Results: We discovered slow degeneration through necroptosis in the Aki2 postmitotic forebrain mutants and dysregulation of many p53 target genes in both transcriptomics datasets. Reduction of the p53 gene in the CaMK-Cre;Aki2fl/fl line delays cell death; while knockout prevents it entirely. Conclusion: This study provides insight into the molecular mechanisms of Aki2 function in cortical neurons and identifies p53 as a molecular mediator of neuronal death in the absence of Aki2. Futhermore, it identifies several candidate Aki2-dependent genes dysregulated in both transcroptomic datasets and many candidate Aki2 target genes that are context dependent.
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Project description:Gene expression microarray analysis was performed on E15.5 p53+/+ and p53-/- litter-matched kidneys. We have previously shown that p53 is expressed in both UB and MM lineages in the kidney, and that p53-null embryos on C57B6L background exhibit a range of congenital abnormalities of the kidney and urinary tract such as duplicated ureters, reduced nephron numbers, and compromised nephron progenitor renewal and differentiation. Here our goal was to reveal the p53 transcriptome in mouse embryonic kidneys at E15.5.
2013-09-05 | GSE49878 | GEO
Project description:Assembly of transcriptomes encoding unique neuronal identities requires selective accessibility of transcription factors to cis-regulatory sequences in nucleosome-embedded postmitotic chromatin. Yet, the mechanisms controlling postmitotic neuronal chromatin accessibility are poorly understood. Here, we show that unique distal enhancers define the Pet1 neuron lineage that generates serotonin (5-HT) neurons. Heterogeneous single cell chromatin landscapes are established early in postmitotic Pet1 neurons and reveal the putative regulatory programs driving Pet1 neuron subtype identities. Distal enhancer accessibility is highly dynamic as Pet1 neurons mature, suggesting the existence of regulatory factors that reorganize postmitotic neuronal chromatin. We find that Pet1 and Lmx1b control chromatin accessibility to select Pet1-lineage specific enhancers for 5-HT neurotransmission. Additionally, these factors are required to maintain chromatin accessibility during early maturation suggesting that postmitotic neuronal open chromatin is unstable and requires continuous regulatory input. Together our findings reveal postmitotic transcription factors that reorganize accessible chromatin for neuron specialization.
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