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Series GSE134233 Query DataSets for GSE134233
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
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.
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 .
Contributor(s) David CJ, Li Y, He Y
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Submission date Jul 12, 2019
Last update date Jul 13, 2020
Contact name Yi He
Organization name Tsinghua university
Street address 30 Shuangqing Rd, Haidian Qu, Beijing Shi, China
City Beijing
ZIP/Postal code 100084
Country China
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (33)
GSM3940100 Fosl1_input_ChIP
GSM3940101 Fosl1+KrasG12D_ChIP
GSM3940102 Foxa2-KrasG12D_ChIP
This SubSeries is part of SuperSeries:
GSE134236 Mutant Kras co-opts a progenitor-derived enhancer network to initiate pancreatic tumorigenesis
BioProject PRJNA554366
SRA SRP214496

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE134233_RAW.tar 3.7 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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