Effect of CBL0137 on nascent transcription in HT1080 cells [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA420940 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6340104.fastq.gz | Fastqsanger.gz | |||
| SRR6340105.fastq.gz | Fastqsanger.gz | |||
| SRR6340106.fastq.gz | Fastqsanger.gz | |||
| SRR6340107.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Small molecule curaxin CBL0137 has broad anti-cancer activity in different preclinical models. It interferes with histone-DNA interactions via binding to DNA without causing DNA damage. It resposents first in class "chromatin damaging" agent without genotoxic properties. Its effect on the transcription in human tumor cells was evaluated. DNA-targeting small molecules are widely used for anticancer therapy based on their ability to induce cell death, presumably via DNA damage. DNA in the eukaryotic cell is packed into chromatin, a highly-ordered complex of DNA, histones, and non-histone proteins. These agents perturb chromatin organization. However, the mechanisms, consequences, and impact of the alterations of chromatin structure in relation to their anti-cancer activity is unclear because it is difficult to separate DNA damage and chromatin damage in cells. We recently demonstrated that curaxins, small molecules with broad anticancer activity, bind DNA without causing detectable DNA damage by interfering with histone/DNA interactions and destabilizing the nucleosome. Chromatin unfolding caused by curaxins is sensed by histone chaperone FACT. FACT binds unfolded nucleosomes, which leads to chromatin trapping or c-trapping. In this study, we investigated whether other DNA-targeting small molecules disturb chromatin and cause c-trapping. We found that only compounds directly binding DNA induce chromatin damage and c-trapping. Chromatin damage may occur in the absence of DNA damage and is dependent on the mechanism of compound binding to DNA and its ability to bind chromatinized DNA in cells. We show that FACT is sensitive to a plethora of nucleosomes perturbations induced by DNA-binding small molecules, including displacement of the linker histone, eviction of core histones, and accumulation of negative supercoiling. Most importantly, the cytotoxicity of DNA-binding small molecules correlates with their ability to cause chromatin damage , but not DNA damage.
2018-03-13 | GSE107633 | GEO
Project description:Effect of CBL0137 on DIPG cells
| PRJNA644393 | ENA
Project description:Diffuse intrinsic pontine glioma (DIPG) is an aggressive and incurable childhood brain tumor for which new treatments are needed. A high throughput drug screen of 3600 pharmaceutical compounds found that anti-malarials, including quinacrine had potent activity against DIPG neurospheres. CBL0137 is a novel anti-cancer compound developed from quinacrine, which targets Facilitates Chromatin Transcription (FACT), a chromatin remodelling complex involved in transcription, replication, and DNA repair. We have found that CBL0137 displays profound cytotoxic activity against a panel of patient derived DIPG cultures, inhibiting cell proliferation and clonogenic potential, restoring tumor suppressor TP53 and Rb activity and inducing cell death through induction of apoptosis. Moreover, in an orthotopic model of DIPG, treatment with CBL0137 significantly extended animal survival. Histone mutations leading to the loss of histone trimethylation result in epigenetic dysregulation driving DIPG tumorigenesis. Treatment with CBL0137 targets this epigenetic defect, restoring both histone H3.3 acetylation and trimethylation and leading to tumor cell death. Combined epigenetic treatment with the histone deacetylase (HDAC) inhibitor panobinostat led to inhibition of the Rb/E2F1 pathway, and increased the enzymatic activity of enhancer of zeste homolog 2 (EZH2), leading to the restoration of H3K27 trimethylation. This combination therapy had synergistic activity against DIPG neurospheres with induction of apoptosis. Consistent with the in vitro results, the combination of CBL0137 and panobinostat significantly prolonged the survival of mice bearing DIPG orthografts suggesting a potential treatment strategy for DIPG.
2021-03-07 | GSE153883 | GEO
Project description:CBL0137 is chromatin destabilizing agent, which causing trapping of FACT histone chaperone in chromatin (Gasparian et all, Science TM, 2011, Safina et all, NAR, 2017). We compared effect of CBL0137 on gene expression in mouse organs, expressing FACT (testes, spleen ) or not (lung, liver) to figure out what effects of CBL0137 is due to the inhibition of FACT and which are independent of FACT.
2017-08-18 | GSE102769 | GEO
Project description:CBL0137 id non-genotoxic DNA binding compounds which directly destabilizes nucleosomes in cells. Effect of different doses of CBL0137 on the abundance of mRNA was studied in two cell types, multiple myeloma MM1.S and cervical carcinoma HeLa cell.
2018-07-25 | GSE117611 | GEO
Project description:We analyzed changes in abundance of RNAs in mouse embryonic fibroblasts (MEF) from wild type and p53 knockout mice and in lungs of NIH Swiss mice upon treatment with 1microM (cells) or 60mg/kg IV (mice) of curaxin CBL0137 for 24 hours. CBL0137 is chromatin destabilizing agent.
2017-08-18 | GSE102768 | GEO
Project description:Effect of HDAC inhibition on nascent transcription by RNAPII in fission yeast
| PRJNA413554 | ENA
Project description:Diffuse intrinsic pontine glioma (DIPG) is an aggressive and incurable childhood brain tumor for which new treatments are needed. A high throughput drug screen of 3600 pharmaceutical compounds found that anti-malarials, including quinacrine had potent activity against DIPG neurospheres. CBL0137 is a novel anti-cancer compound developed from quinacrine, which targets Facilitates Chromatin Transcription (FACT), a chromatin remodelling complex involved in transcription, replication, and DNA repair. We have found that CBL0137 displays profound cytotoxic activity against a panel of patient derived DIPG cultures, inhibiting cell proliferation and clonogenic potential, restoring tumor suppressor TP53 and Rb activity and inducing cell death through induction of apoptosis. Moreover, in an orthotopic model of DIPG, treatment with CBL0137 significantly extended animal survival. Histone mutations leading to the loss of histone trimethylation result in epigenetic dysregulation driving DIPG tumorigenesis. Treatment with CBL0137 targets this epigenetic defect, restoring both histone H3.3 acetylation and trimethylation and leading to tumor cell death. Combined epigenetic treatment with the histone deacetylase (HDAC) inhibitor panobinostat led to inhibition of the Rb/E2F1 pathway, and increased the enzymatic activity of enhancer of zeste homolog 2 (EZH2), leading to the restoration of H3K27 trimethylation. This combination therapy had synergistic activity against DIPG neurospheres with induction of apoptosis. Consistent with the in vitro results, the combination of CBL0137 and panobinostat significantly prolonged the survival of mice bearing DIPG orthografts suggesting a potential treatment strategy for DIPG.
2021-02-12 | GSE153441 | GEO
Project description:Nascent transcription during NuRD complex induction
| PRJEB26876 | ENA
Project description:Radiotherapy and IFNγ treatment effect on transcriptome in HT1080 cells
| PRJNA573927 | ENA