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| Status |
Public on Jul 11, 2020 |
| Title |
Mutant Kras co-opts a progenitor-derived enhancer network to initiate pancreatic tumorigenesis [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Oncogenes are highly specific in the cells they can transform, although the molecular basis for this is poorly understood. Inflammation often promotes tumorigenesis, and in the pancreas it promotes cellular plasticity and accelerates Kras-driven neoplasia. We demonstrate that plasticity is coupled to the emergence of transient progenitor cells that are readily transformed by KrasG12D. The progenitor state is linked to coordinate upregulation of proliferation genes through chromatin opening at nearby lineage-specific enhancers. Mutant Kras taps into this program by co-opting the normally transient enhancer elements, making them permanent and Kras-dependent in cancer. Mechanistically, co-option occurs through cooperation of Kras-driven transcription factors with the existing landscape of pancreatic lineage transcription factors, which are recruited to play a central role in driving the mutant Kras-dependent transcriptional program. These observations suggest that proliferation is controlled by tissue-specific enhancer networks that are tapped into by oncogenes, helping explain the lineage specificity of cancer drivers.
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| Overall design |
Examination of
[1] 2 different histone modifications and 4 different transcription factors in PDA cell line.
[2] H3K27ac histone modifications in two different types of PDA cell line by using MEK inhibitors or AKT inhibitor treatment.
[3] Klf5 and Foxa2 in PDA cell line by Junb and Fosl1 overexpression .
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| Contributor(s) |
David CJ, Li Y, He Y |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jul 12, 2019 |
| Last update date |
Jul 13, 2020 |
| Contact name |
Yi He |
| E-mail(s) |
sonichy@126.com
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| Organization name |
Tsinghua university
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| Street address |
30 Shuangqing Rd, Haidian Qu, Beijing Shi, China
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| City |
Beijing |
| ZIP/Postal code |
100084 |
| Country |
China |
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| Platforms (1) |
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| Samples (33)
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| This SubSeries is part of SuperSeries: |
| GSE134236 |
Mutant Kras co-opts a progenitor-derived enhancer network to initiate pancreatic tumorigenesis |
|
| Relations |
| BioProject |
PRJNA554366 |
| SRA |
SRP214496 |
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