Determine whether AsiDNA and belinostat alter H1.2 occupancy genome-wide. [ChIP-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1107964 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28903133_1.fastq.gz | Fastqsanger.gz | |||
| SRR28903133_2.fastq.gz | Fastqsanger.gz | |||
| SRR28903134_1.fastq.gz | Fastqsanger.gz | |||
| SRR28903134_2.fastq.gz | Fastqsanger.gz | |||
| SRR28903135_1.fastq.gz | Fastqsanger.gz |
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Project description:An effective long-term inhibition of multiple DNA repair signals is required to design a novel and effective therapeutic for glioblastoma (GBM), a highly DNA repair ‘addicted’ cancer. AsiDNA, a double-strand DNA break (DSB) mimetic, is an innovative approach that shuts down the entire DNA repair system in cancer cells by sequestering DSB repair factors. We showed that inhibition of class I histone deacetylases (HDACs) dislodges repair factors from sites of DNA damage. We therefore tested whether AsiDNA and pan HDAC inhibitor Belinostat combination can impart a chromatin-based long-term DNA damage and impair DNA repair in GBM cells. We performed mass spectrometry with chromatin isolated from AsiDNA and Belinostat and found that Belinostat reduces histone H1.2 levels. To this end, we assessed whether AsiDNA and Belinostat alter histone H1.2 occupancy genome-wide. In order to understand the long-term effects of AsiDNA on DNA repair, we treated U87 cells with AsiDNA for 6 days followed by 6 days recovery from the drug. We used this protocol to create long-term AsiDNA treated cells (LTAU87) according to the clinical trial protocol. We performed H1.2 ChIP-Seq with LTAU87 cells and MTU87 (mock treated U87; control) in the presence and absence of belinostat in order to address whether they alter the global chromatin structure.
2024-05-13 | GSE266619 | GEO
Project description:An effective long-term inhibition of multiple DNA repair signals is required to design a novel and effective therapeutic for glioblastoma (GBM), a highly DNA repair ‘addicted’ cancer. AsiDNA, a double-strand DNA break (DSB) mimetic, is an innovative approach that shuts down the entire DNA repair system in cancer cells by sequestering DSB repair factors. We showed that inhibition of class I histone deacetylases (HDACs) dislodges repair factors from sites of DNA damage. We therefore tested whether AsiDNA and pan HDAC inhibitor Belinostat combination can impart a chromatin-based long-term DNA damage and impair DNA repair in GBM cells. We performed mass spectrometry with chromatin isolated from AsiDNA and Belinostat and found that Belinostat reduces histone H1.2 levels. To this end, we assessed whether AsiDNA and Belinostat alter histone H1.2 occupancy genome-wide. In order to understand the long-term effects of AsiDNA on DNA repair, we treated U87 cells with AsiDNA for 6 days followed by 6 days recovery from the drug. We used this protocol to create long-term AsiDNA treated cells (LTAU87) according to the clinical trial protocol. We performed NicE-seq with LTAU87 cells and MTU87 (mock treated U87; control) in the presence or absence of belinostat treatment in order to address whether they alter the global chromatin structure.
2024-05-13 | GSE266621 | GEO
Project description:Determine whether AsiDNA and belinostat alter chromatin accessbility genome-wide in glioblastoma cells. [NicE-Seq]
| PRJNA1107962 | ENA
Project description:An effective long-term inhibition of multiple DNA repair signals is required to design a novel and effective therapeutic for glioblastoma (GBM), a highly DNA repair ‘addicted’ cancer. AsiDNA, a double-strand DNA break (DSB) mimetic, is an innovative approach that shuts down the entire DNA repair system in cancer cells by sequestering DSB repair factors. We showed that inhibition of class I histone deacetylases (HDACs) dislodges repair factors from sites of DNA damage. We therefore tested whether AsiDNA and pan HDAC inhibitor Belinostat combination can impart a chromatin-based long-term DNA damage and impair DNA repair in GBM cells. In order to understand the long-term effects of AsiDNA on DNA repair, we treated U87 cells with AsiDNA for 6 days followed by 6 days recovery from the drug. We used this protocol to create long-term AsiDNA treated cells (LTAU87) according to the clinical trial protocol. We performed RNA-Seq with LTAU87 cells and MTU87 (mock treated U87; control) in the presence and absence of belinostat.
2024-05-13 | GSE266620 | GEO
Project description:Effect of AsiDNA and belinostat on gene expression in U87 cells. [RNA-Seq]
| PRJNA1107963 | ENA
Project description:Increasing evidence suggests that linker histone H1 can influence distinct cellular processes by acting as a gene-specific regulator. However, the mechanistic basis underlying such H1 specificity and whether H1 acts in concert with other chromatin-altering activities remain unclear. To investigate the cooperative role of H1.2, Cul4A and PAF1 on gene regulation, genome-wide gene expression analysis is carried out in 293T cells expressing control shRNA, H1.2 shRNA, Cul4A shRNA or PAF1 shRNA. Total RNA was isolated from 293T cells expressing NCsh, H1.2sh, Cul4Ash, or PAF1sh
2013-12-20 | E-GEOD-52544 | biostudies-arrayexpress
Project description:Transcriptome analysis revealed a major change in gene expression with a large excess of genes down regulated in 3 independent AsiDNA-treated “evolved” populations as compared to three independent not-treated “naïve” populations The Achilles heel of anticancer treatments is intrinsic or acquired resistance. Among many targeted therapies, the DNA repair inhibitors show limited efficacy due to rapid emergence of resistance. We examined evolution of cancer cells and tumors treated with AsiDNA, a new DNA repair inhibitor targeting all DNA break repair pathways. Effects of AsiDNA or Olaparib were analyzed in various cell lines. Frequency of AsiDNA- and olaparib-resistant clones was measured after 2 weeks of continuous treatment in KBM7 haploid cells. Cell survivals were also measured after one to six cycles of 1-week treatment and 1-week recovery in MDA-MB-231 and NCI-H446. Transcriptomes of cell populations recovering from cyclic treatments or mock treatment were compared. MDAMB- 231 xenografted models were treated with three cycles of AsiDNA to monitor the effects of treatment on tumor growth and transcriptional modifications. No resistant clones were selected after AsiDNA treatment (frequency b 3x10−8) in treatment conditions that generate resistance to olaparib at a frequency of 7.2x10−7 resistant clones per treated cell. Cyclic treatments promote cumulative sensitivity characterized by a higher mortality of cells having undergone previous treatment cycles. This sensitization was stable, and transcriptome analysis revealed a major gene downregulation with a specific overrepresentation of genes coding for targets of DNA-PK. Such changes were also detected in tumor models which showed impaired growth after cycles of AsiDNA treatment.
2020-08-20 | GSE144023 | GEO
Project description:Increasing evidence suggests that linker histone H1 can influence distinct cellular processes by acting as a gene-specific regulator. However, the mechanistic basis underlying such H1 specificity and whether H1 acts in concert with other chromatin-altering activities remain unclear. To investigate the cooperative role of H1.2, Cul4A and PAF1 on gene regulation, genome-wide gene expression analysis is carried out in 293T cells expressing control shRNA, H1.2 shRNA, Cul4A shRNA or PAF1 shRNA.
2013-12-20 | GSE52544 | GEO
Project description:Linker histone H1 is a protein component of chromatin and has been linked to chromatin compaction and global gene silencing.It has been sugegsted that H1 plays a significant role, regulating a relatively small number of genes. Here we show that H1.2- a variant of H1 subtype is recruited to chromatin region and is dependent on EZH2-mediated H3K27me3. Therefore a Gene expression array analysis was carried out with H1.2 as well as EZH2 knockout MCF7 cells to confirm the interlationship of H1.2 and EZH2 activity. Total RNA was isolated from MCF7 cells in which EZH2 and H1.2 genes have been depleted along with the wild type cells to study the differential regulation of various genes in each case.
2015-12-21 | E-GEOD-68050 | biostudies-arrayexpress
Project description:AsiDNA, a cholesterol-coupled oligonucleotide mimicking double-stranded DNA breaks, was developed to sensitize tumour cells to radio- and chemotherapy. This drug acts as a decoy hijacking the DNA damage response. Previous studies have demonstrated that standalone AsiDNA administration is well tolerated with no additional adverse effects when combined with chemo- and/or radiotherapy. This lack of normal tissue complication encouraged further examination into the role of AsiDNA in normal cells. The delayed development of pulmonary fibrosis after FLASH-RT compared to CONV-RT might be a known phenomenon but the complexity behind this specific tissue response is completely unidentified. Radiation has been shown to impact various cell types presented in the lung, resulting in changes in cellular activity and numerous pathway activations. Current unpublished data suggest a clear variety between the CONV and FLASH-RT gene signatures examined using single cell RNA sequencing. As the combined treatment of AsiDNA with CONV-RT resulted in a delay in radiation induced lung fibrosis compared to CONV-RT standalone, it is to be questioned if the signature of AsiDNA CONV-RT is similar to FLASH-RT or CONV-RT. To characterize the similarity in cellular changes and expression signatures in lungs 5 months post CONV-RT, FLASH-RT, AsiDNA CONV-RT or non-irradiated (Control) treatment. Single cell RNA sequencing of irradiated lungs revealed a closer resemblance between CONV AsiDNA and FLASH-RT in profibrotic gene signatures within the fibroblast and macrophages population, in comparison to CONV-RT standalone. Collectively, this information indicates that the activity of AsiDNA and FLASH-RT could draw upon identical mechanism interference to result in the protective capacities within the normal tissue.
2024-02-27 | GSE240510 | GEO