Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1208284 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR31939347_1.fastq.gz | Fastqsanger.gz | |||
| SRR31939347_2.fastq.gz | Fastqsanger.gz | |||
| SRR31939348_1.fastq.gz | Fastqsanger.gz | |||
| SRR31939348_2.fastq.gz | Fastqsanger.gz |
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Project description:The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA damage response, an inducible process required for the suppression of malignancy. The Mre11 complex is predominantly required for repair and checkpoint activation in S phase, while Chk2 governs apoptosis. We examined the relationship between the Mre11 complex and Chk2 in the DNA damage response via the establishment of Nbs1âB/âB Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice. Chk2 deficiency did not modify the checkpoint defects or chromosomal instability of Mre11 complex mutants; however, the double mutant mice exhibited synergistic defects in DNA damage-induced p53 regulation and apoptosis. Nbs1âB/âB Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice were also predisposed to tumors. In contrast, DNA-PKcs deficient mice, in which G1-specific chromosome breaks are present, did not exhibit synergy with Chk2-/- mutants. These data suggest that Chk2 suppresses the oncogenic potential of DNA damage arising during S and G2 phases of the cell cycle. Experiment Overall Design: Thymocytes from Wild type (Wt), Atm-/- and Chk2-/- mice were exposed to mock 5 Gy radiation (IR). The RNA was harvested 8 hours post treatment.
2008-06-20 | E-GEOD-11436 | biostudies-arrayexpress
Project description:The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA damage response, an inducible process required for the suppression of malignancy. The Mre11 complex is predominantly required for repair and checkpoint activation in S phase, while Chk2 governs apoptosis. We examined the relationship between the Mre11 complex and Chk2 in the DNA damage response via the establishment of Nbs1∆B/∆B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice. Chk2 deficiency did not modify the checkpoint defects or chromosomal instability of Mre11 complex mutants; however, the double mutant mice exhibited synergistic defects in DNA damage-induced p53 regulation and apoptosis. Nbs1∆B/∆B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice were also predisposed to tumors. In contrast, DNA-PKcs deficient mice, in which G1-specific chromosome breaks are present, did not exhibit synergy with Chk2-/- mutants. These data suggest that Chk2 suppresses the oncogenic potential of DNA damage arising during S and G2 phases of the cell cycle. Keywords: Global gene expression analysis, response to radiation, Nbs1∆B/∆B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mutant mice
2008-05-15 | GSE11436 | GEO
Project description:The functional status of mitochondria is relayed by mitochondrial retrograde signaling (MRS) to elicit adaptive changes in nuclear gene expression. However, MRS pathways that sense the amount of the multi-copy mitochondrial DNA (mtDNA) in mammalian cells remain poorly understood. Budding yeast have “intergenomic signaling” pathways that can sense the amount of mtDNA independently of oxidative phosphorylation (OXPHOS), the primary function of genes encoded by mtDNA. We found that mtDNA-depleted IMR90 cells can sustain OXPHOS for a significant amount of time, providing a robust model system to interrogate human intergenomic signaling. FAM43A is induced early in response to mtDNA depletion in a CHK2 kinase-dependent manner, and its depletion activates CHK2 to increase mtDNA copy number via upregulation of the p53R2 form of ribonucleotide reductase. We propose that FAM43A serves a checkpoint-like function that restricts mtDNA replication in the presence of mtDNA stress to maintain mtDNA integrity. FAM43A could be a candidate mtDNA-disease locus and a therapeutic target for mtDNA depletion syndromes.
2025-01-16 | GSE273181 | GEO
Project description:EDM2 is a PHD finger-containing histone binding protein in Arabidopsis thaliana (Arabidopsis) that affects levels of the transposon silencing mark H3K9me2. Here we report on genome-wide profiling by ChIP-seq and RNA-seq of EDM2-mediated effects on H3K9me2 and rRNA-depleted transcripts, respectively. EDM2 affects H3K9me2 and/or transcript levels at hundreds transposons and over 3000 gene loci including 60 NLR genes. In addition, EDM2 also binds to several NLR genes and transposons.
2020-08-03 | GSE108487 | GEO
Project description:The piRNA pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. piRNAs are maternally deposited and required for proper transposon silencing in adult offspring. However, a long-standing question in the field is the precise function of maternally deposited piRNAs and its associated factors during embryogenesis. Here, we probe the spatio-temporal expression patterns of several piRNA pathway components during early stages of development. Amongst those, factors required for transcriptional gene silencing (TGS) showed ubiquitous abundance in somatic and pole cells throughout the first half of embryogenesis. We further analysed the transcriptomes of various embryo stages and correlated these with the presence of selected chromatin marks. We found that a number of transposon families show bursts of transcription during early embryonic stages. Transposons heavily targeted by maternally deposited piRNAs accumulated repressive chromatin marks following their spike in expression. Furthermore, depletion of maternally deposited Piwi protein in early embryos resulted in increased expression of transposons targeted by inherited piRNAs and was accompanied by a strong loss of repressive chromatin marks at coding sequences. Overall, our data suggests a pivotal role for the piRNA pathway in transposon defence during Drosophila embryogenesis in somatic cells.
2021-07-26 | PXD022409 | Pride
Project description:Circadian rhythms allow organisms to adjust to daily environmental fluctuations. The interplay between the circadian clock, the cell cycle, and DNA repair has been extensively documented, yet the epigenetic control of the circadian clock by the DNA damage response pathway remains relatively unexplored. Here, we showed that checkpoint kinases CHK1 and CHK2 regulate chromatin structure under DNA damage stress in Neurospora crassa to maintain robust circadian rhythms. Under DNA damage stress, deletion of chk1 and chk2 disrupted the rhythmic transcription of the clock gene frq by suppressing the rhythmic binding of the transcription activator WCC at the frq promoter, as the chromatin structure remained condensed. Mechanistically, CHK1 and CHK2 interacted and bound at the frq promoter to phosphorylate H3T11, promoting H3 acetylation, especially H3K56 acetylation, to counteract the histone variant H2A.Z deposition, establishing a suitable chromatin state to maintain the robust circadian rhythm despite DNA damage. Additionally, a genome-wide correlation was discovered between H3T11 phosphorylation and H3K56 acetylation, showing a specific function at the frq promoter that is dependent on CHK1 and CHK2. Furthermore, transcriptome analysis revealed that CHK1 and CHK2 are responsible for robust rhythmic transcription of metabolic and DNA repair genes under DNA damage stress. These findings highlight the essential role of checkpoint kinases in maintaining robust circadian rhythms under DNA damage stress.
2025-02-16 | GSE273616 | GEO
Project description:The piRNA pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. piRNAs are maternally deposited and required for proper transposon silencing in adult offspring. However, a long-standing question in the field is the precise function of maternally deposited piRNAs and its associated factors during embryogenesis. Here, we probe the spatio-temporal expression patterns of several piRNA pathway components during early stages of development. Amongst those, factors required for transcriptional gene silencing (TGS) showed ubiquitous abundance in somatic and pole cells throughout the first half of embryogenesis. We further analyzed the transcriptomes of various embryo stages and correlated these with the presence of selected chromatin marks. We found that a number of transposon families show bursts of transcription during early embryonic stages. Transposons heavily targeted by maternally deposited piRNAs accumulated repressive chromatin marks following their spike in expression. Furthermore, depletion of maternally deposited Piwi protein in early embryos resulted in increased expression of transposons targeted by inherited piRNAs and was accompanied by a strong loss of repressive chromatin marks at coding sequences. Overall, our data suggests a pivotal role for the piRNA pathway in transposon defence during Drosophila embryogenesis in somatic cells.
2021-07-22 | GSE160778 | GEO
Project description:Background and aims: A coordinated stress and regenerative response is important following hepatocyte damage. Here, we investigate the phenotypes that result from genetic abrogation of individual components of the CHK2/ p53/ p21 pathway in a murine model of metabolic liver injury. Methods: NTBC was reduced or withdrawn in FAH-/- mice lacking Chk2, p53 or p21, and survival, tumor development, liver injury and regeneration were analyzed. Partial hepatectomies were performed and mice were challenged with the Fas-antibody Jo2. Results: In a model of metabolic liver injury, loss of p53, but not of Chk2, impairs the oxidative stress re-sponse and aggravates liver damage, indicative of a direct p53-dependent protective effect on hepatocytes. Cell cycle control during chronic liver injury critically depends on the presence of both p53 and its downstream effector p21. In p53-deficient hepatocytes, unchecked proliferation occurs despite a strong induction of p21, revealing a complex interdependency between p21 and p53. The increased regenerative potential in the absence of p53 cannot fully compensate the surplus injury and is not sufficient to promote survival. Despite the different phenotypes as-sociated with the loss of individual components of the DNA damage response, gene expression patterns are dominated by the severity of liver injury, but reflect distinct effects of p53 on prolif-eration and the anti-oxidative stress response. Conclusion: Characteristic phenotypes result from the genetic abrogation of individual components of the DNA damage response cascade in a liver injury model. The extent to which loss of gene function can be compensated, or affects injury and proliferation, depends on the level at which the cas-cade is interrupted.
2021-04-02 | GSE156981 | GEO
Project description:Background and aims: A coordinated stress and regenerative response is important following hepatocyte damage. Here, we investigate the phenotypes that result from genetic abrogation of individual components of the CHK2/ p53/ p21 pathway in a murine model of metabolic liver injury. Methods: NTBC was reduced or withdrawn in Fah / mice lacking Chk2, p53 or p21, and survival, tumor development, liver injury and regeneration were analyzed. Partial hepatectomies were performed and mice were challenged with the Fas-antibody Jo2. Results: In a model of metabolic liver injury, loss of p53, but not of Chk2, impairs the oxidative stress re-sponse and aggravates liver damage, indicative of a direct p53-dependent protective effect on hepatocytes. Cell cycle control during chronic liver injury critically depends on the presence of both p53 and its downstream effector p21. In p53-deficient hepatocytes, unchecked proliferation occurs despite a strong induction of p21, revealing a complex interdependency between p21 and p53. The increased regenerative potential in the absence of p53 cannot fully compensate the surplus injury and is not sufficient to promote survival. Despite the different phenotypes as-sociated with the loss of individual components of the DNA damage response, gene expression patterns are dominated by the severity of liver injury, but reflect distinct effects of p53 on prolif-eration and the anti-oxidative stress response. Conclusion: Characteristic phenotypes result from the genetic abrogation of individual components of the DNA damage response cascade in a liver injury model. The extent to which loss of gene function can be compensated, or affects injury and proliferation, depends on the level at which the cas-cade is interrupted.
2021-04-02 | GSE156251 | GEO