Ma et al. 2020 (PRJNA532532)
General Details
| Title | Super-enhancer redistribution as a mechanism of broad gene dysregulation in repeatedly drug-treated cancer cells [dataset 2] |
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| Organism | |
| Number of Samples | 4 |
| Release Date | 2019/04/12 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP192310 |
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| ENA | SRP192310 |
| GEO | |
| BioProject | PRJNA532532 |
Publication
| Title | |
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| Authors | Ma Q,Yang F,Mackintosh C,Jayani RS,Oh S,Jin C,Nair SJ,Merkurjev D,Ma W,Allen S,Wang D,Almenar-Queralt A,Garcia-Bassets I |
| Journal | Cell reports |
| Publication Date | 2020 Apr 21 |
| Abstract | Cisplatin is an antineoplastic drug administered at suboptimal and intermittent doses to avoid life-threatening effects. Although this regimen shortly improves symptoms in the short term, it also leads to more malignant disease in the long term. We describe a multilayered analysis ranging from chromatin to translation-integrating chromatin immunoprecipitation sequencing (ChIP-seq), global run-on sequencing (GRO-seq), RNA sequencing (RNA-seq), and ribosome profiling-to understand how cisplatin confers (pre)malignant features by using a well-established ovarian cancer model of cisplatin exposure. This approach allows us to segregate the human transcriptome into gene modules representing distinct regulatory principles and to characterize that the most cisplatin-disrupted modules are associated with underlying events of super-enhancer plasticity. These events arise when cancer cells initiate without ultimately ending the program of drug-stimulated death. Using a PageRank-based algorithm, we predict super-enhancer regulator ISL1 as a driver of this plasticity and validate this prediction by using CRISPR/dCas9-KRAB inhibition (CRISPRi) and CRISPR/dCas9-VP64 activation (CRISPRa) tools. Together, we propose that cisplatin reprograms cancer cells when inducing them to undergo near-to-death experiences. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved. |
| PMC | |
| PMID | 32320655 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR8887170 | PRJNA532532 | Homo sapiens | A2780 | Ribo-Seq |  |
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| SRR8887171 | PRJNA532532 | Homo sapiens | A2780 | Ribo-Seq | |
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| SRR8887172 | PRJNA532532 | Homo sapiens | A2780 | Ribo-Seq | |
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| SRR8887173 | PRJNA532532 | Homo sapiens | A2780 | Ribo-Seq | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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