Similar Datasets
Project description:Genotoxicants have been used for decades as front-line therapies against cancer on the basis of their DNA-damaging actions. However, some of their non-DNA-damaging effects are also instrumental for killing dividing cells. We report here that the anthracycline Daunorubicin (DNR) but not the nucleoside analog Cytarabine, the two main drugs used to treat Acute Myeloid Leukemia (AML), induces rapid (3 hours) and broad transcriptional changes in AML cells. The regulated genes are particularly enriched in genes controlling cell proliferation and death, as well as inflammation and immunity. These transcriptional changes are preceded by DNR-dependent deSUMOylation of chromatin proteins, in particular at active promoters and enhancers. Surprisingly, accelerating deSUMOylation dampens DNR-induced transcriptional reprogramming. Quantitative proteomics shows that proteins that are deSUMOylated in response to DNR are mostly transcription factors, transcriptional co-regulators and chromatin organizers. Among them, the CCCTC-binding factor CTCF is highly enriched at SUMO-binding sites found in cis-regulatory regions. This is notably the case at the promoter of the DNR-induced NFKB2 gene. Although DNR does not modify CTCF binding on chromatin in general and at NFKB2 promoter in particular, it leads to a SUMO-dependent reconfiguration of chromatin loops engaging CTCF- and SUMO-bound NFKB2 promoter with distal cis-regulatory regions.
2023-06-23 | GSE231023 | GEO
Project description:Genotoxicants have been used for decades as front-line therapies against cancer on the basis of their DNA-damaging actions. However, some of their non-DNA-damaging effects are also instrumental for killing dividing cells. We report here that the anthracycline Daunorubicin (DNR), one of the main drugs used to treat Acute Myeloid Leukemia (AML), induces broad transcriptional changes in AML cells before cell death induction. The regulated genes are particularly enriched in genes controlling cell proliferation and death, as well as inflammation and immunity. These transcriptional changes are preceded by DNR-dependent deSUMOylation of chromatin proteins, which limits both the positive and negative effects of DNR on transcription. Quantitative proteomics shows that proteins that are deSUMOylated in response to DNR are mostly transcription factors, transcriptional co-regulators and chromatin organizers. Among them, the CCCTC-binding factor CTCF is highly enriched at SUMO-binding sites found in cis-regulatory regions. This is notably the case at the promoter of the DNR-induced NFKB2 gene. Its induction is preceded by a SUMO-dependent reconfiguration of chromatin loops engaging its CTCF- and SUMO-bound promoter with distal cis-regulatory regions. Altogether, our work suggests that one of the earliest effects of DNR in AML cells is a SUMO-dependent transcriptional reprogramming.
2023-06-23 | PXD032956 | Pride
Project description:Acute Myeloid Leukemia cell line HL-60 were treated with 1 M daunorubicin (DNR) or 2M cytarabin (Ara-C) or 1 M DNR + 10 M VAS2870 (NADPH oxidase inhibitor) for 2 hours. ChIP-Seq experiments were carried out with SUMO-2/3 antibodies. Immunoprecipitated DNA and corresponding inputs from 3 independent experiments were pooled and processed for deep-sequencing (Hi-SEq 2000, Illumina).
2023-12-30 | E-MTAB-4947 | biostudies-arrayexpress
Project description:Daunorubicin (DNR) and Cytarabin (Ara-C) are the main chemotherapeutic drugs used for Acute Myeloid Leukemias (AML) treatment. However, their mode of action is not well understood. To decipher if these drug would induce rapid transcriptional reprogramming, we treated HL-60 AML cell line with DNR or Ara-C for 3 hours and carried out a transcriptomic analyses. In addition, we had shown that Reactive Oxigen Species (ROS) produced by NADPH oxidases (NOX) are involved in DNR-induced gene expression. We therefore also performed a transcriptomic analyses in HL-60 cells treated with DNR and VAS2870, an NADPH oxidase inhibitor. HL-60 cells were treated or not for 3 hours with 2 µM Ara-C, 1 µM DNR or 1 µM DNR + 20µM VAS 2870. RNAs were purified from 3 independent experiments and used to probe Affymetrix Human Gene 2.0 ST Genechips
2017-12-31 | E-MTAB-4895 | biostudies-arrayexpress
Project description:Donminant negative transform growth factor receptor II (DNR) mice were served as a murine primary biliary cirrhrosis model. CD4+Foxp3+ Regulatory T cells (Tregs) play a critical role in self-tolerance and in regulating PBC. In order to determine whether DNR mice derived Tregs processed defective function compared with WT Tregs, CD4+Foxp3+ Treg cells were sorted from DNR and WT mice, respectively, then gene expression analysis was performed by using the Affymetrix GeneChip Mouse Genome 430 2.0 arrays CD4+Foxp3+ Tregs were sorted from the spleen of 10-week-old DNR mice and B6 wild-type mice, respectively. RNA of each sample was then extracted and hybridized on Affymetrix microarrays to detail differences between DNR Tregs and WT Tregs in gene expression.
2014-11-05 | E-GEOD-62964 | biostudies-arrayexpress
Project description:Donminant negative transform growth factor receptor II (DNR) mice were served as a murine primary biliary cirrhrosis model. CD4+Foxp3+ Regulatory T cells (Tregs) play a critical role in self-tolerance and in regulating PBC. In order to determine whether DNR mice derived Tregs processed defective function compared with WT Tregs, CD4+Foxp3+ Treg cells were sorted from DNR and WT mice, respectively, then gene expression analysis was performed by using the Affymetrix GeneChip Mouse Genome 430 2.0 arrays
2014-11-05 | GSE62964 | GEO
Project description:DNA microarray analysis was employed to investigate the transcriptome response to nitric oxide in Pseudomonas aeruginosa. We focused on the role played by the nitric oxide-response regulators DNR and FhpR and an oxygen-response regulator ANR in the response. The transcriptome profiles of the P. aeruginosa strains before and after exposure to nitric oxide under the microaerobic conditions were analyzed. Wild type, its anr, dnr, and fhpR mutants, and the anr mutant that express dnr were used for the analyses.
2014-12-08 | GSE58862 | GEO
Project description:Wide inter-individual variation in terms of outcome and toxic side effects of treatment exist among patients with AML receiving chemotherapy with cytarabine (Ara-C) and daunorubicin (Dnr). Drug resistance and relapse are considered major causes of treatment failure. Gene expression profiling was undertaken to address possible mechanisms of Ara-C/Dnr resistance. Based on ex vivo Ara-C cytotoxicity at diagnosis, Ara-C sensitive (IC50 <3uM AraC) and Dnr sensitive samples (IC50 < 0.5 uM) (5 samples each) were included for microarray analysis. These were compared with the samples which were drug resistant ex vivo at diagnosis. Our microarray experiment resulted in indentifying differentially expressed genes under ex vivo Ara-C sensitive as well as Dnr sensitive samples compared to ex vivo Drug resistant samples.
2016-01-02 | GSE52919 | GEO
Project description:Chloride permeability in the thin and thick ascending limbs of the loop of Henle is a crucial component for urine concentration, with ClC-K/barttin chloride channels as a central component in establishing the cortico-medullary osmotic gradient. Barttin is an accessory subunit of human ClC-K channels, promoting trafficking of the ClC-K/barttin complex to the plasma membrane, increasing channel stability, and switching ClC-K/barttin channels into an active state. Barttin undergoes post-translational palmitoylation, which is essential for channel activation. Here, we identified DHHC7 as a major barttin palmitoyl-acyltransferase, the depletion of which reduced barttin palmitoylation and the macroscopic current amplitudes in cells expressing ClC-K/barttin channels. To investigate a functional role of barttin palmitoylation in vivo, we established Zdhhc7-/- mice. Although barttin palmitoylation was significantly decreased in the kidneys of Zdhhc7-/- animals, it did not result in any pathological consequences for kidney structure or function under physiological conditions. However, when Zdhhc7-/- animals were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) Type IV with mild progression. Notably, decreased barttin palmitoylation was also found for the R8L barttin mutant identified in human BS Type IV. These data suggest that barttin palmitoylation plays an important role in chloride channel dysfunction in certain variants of BS. Thus, our study provides evidence of the downregulation of barttin palmitoylation as a possible mechanism in the etiology of BS, making the restoration of barttin palmitoylation a promising clinical strategy for the treatment of Type IV BS.
2020-03-31 | PXD017231 | Pride
Project description:The Acute Myeloid Leukemia cell line HL-60 was rendered resistant to daunorubicin (DNR) or cytarabine (Ara-C) by continuous exposure to the drug up to concentrations of 30nM for DNR and 100nM for Ara-C. Transcriptomic analysis were then performed by RNA-Seq to compare the cell lines
2022-01-08 | GSE193094 | GEO