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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 17, 2023 |
| Title |
Synthetic epigenetic reprogramming of mesenchymal to epithelial states using the CRISPR/dCas9 platform in triple negative breast cancer [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Epithelial-mesenchymal transition (EMT) is a reversible transcriptional program subverted by cancer cells to drive cancer progression. Transcription factor ZEB1 is a master regulator of EMT, driving disease recurrence in poor outcome triple negative breast cancer (TNBC). Here, we silence ZEB1 in TNBC models by CRISPR-mediated epigenetic editing, resulting in nearly complete repression of ZEB1 in vivo, accompanied by long-lasting tumor inhibition. Integrated transcriptomic and epigenetic profiling identified a ZEB1-dependent gene-signature associated with transcriptional up-regulation, promoter DNA demethylation and enhanced chromatin accessibility in core cell adhesion loci, demonstrating epigenetic reprogramming towards a more epithelial state. Epigenetic shifts induced by ZEB1-silencing are enriched in a subset of human breast tumors, illuminating a clinically-relevant hybrid-like state. Thus, the synthetic epi-silencing of ZEB1 induces stable “lock-in” epigenetic reprogramming of mesenchymal tumors associated with a distinct epigenetic landscape. We outline approaches to stably reprogram EMT for targeting poor outcome breast cancers driven by oncogenic transcription factors.
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| Overall design |
Native chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modifications H3K9me3 and H3K4me3 in SUM159 cells with pLV-KRAB and a combination of 4 gRNAs targeting the promoter of ZEB1 or empty vector (control).
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| Contributor(s) |
Charlene W, Cursons J, Pilar B |
| Citation(s) |
37217832 |
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| Submission date |
Aug 01, 2022 |
| Last update date |
Jul 17, 2023 |
| Contact name |
Joe Cursons |
| Organization name |
Monash University
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| Department |
Biomedicine Discovery Institute
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| Street address |
19 Innovation Walk
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| City |
Clayton |
| State/province |
VIC |
| ZIP/Postal code |
3800 |
| Country |
Australia |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| GSM6427514 |
SUM159 pLV-KRAB + all 4-targeting gRNAs, H3K9me3, abcam Ab8898, biol rep 1 |
| GSM6427515 |
SUM159 pLV-KRAB + all 4-targeting gRNAs, H3K9me3, abcam Ab8898, biol rep 2 |
| GSM6427516 |
SUM159 pLV-KRAB + empty vector control, H3K9me3, abcam Ab8898, biol rep 1 |
| GSM6427517 |
SUM159 pLV-KRAB + empty vector control, H3K9me3, abcam Ab8898, biol rep 2 |
| GSM6427518 |
SUM159 pLV-KRAB + all 4-targeting gRNAs, H3K4me3, abcam Ab8580, biol rep 1 |
| GSM6427519 |
SUM159 pLV-KRAB + all 4-targeting gRNAs, H3K4me3, abcam Ab8580, biol rep 2 |
| GSM6427520 |
SUM159 pLV-KRAB + empty vector control, H3K4me3, abcam Ab8580, biol rep 1 |
| GSM6427521 |
SUM159 pLV-KRAB + empty vector control, H3K4me3, abcam Ab8580, biol rep 2 |
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| This SubSeries is part of SuperSeries: |
| GSE210277 |
Synthetic epigenetic reprogramming of mesenchymal to epithelial states using the CRISPR/dCas9 platform in triple negative breast cancer |
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| Relations |
| BioProject |
PRJNA864873 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE210275_RAW.tar |
1.8 Gb |
(http)(custom) |
TAR (of BROADPEAK, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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