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Series GSE134230 Query DataSets for GSE134230
Status Public on Jul 11, 2020
Title Mutant Kras co-opts a progenitor-derived enhancer network to initiate pancreatic tumorigenesis [ATAC-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 chromatin accessiblity of
[1] mCherry-positive cells on day0,day,day7 after CAE injection.
[2] eGFP-positive cells from pancreas after knocking out Kras,Junb,Fosl1,Klf5,Foxa2,Rosa.
[3] mCherry-positive cells from Tamoxifen induced KrasG12D on day7 after CAE injection and the PDA.
 
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
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 (28)
GSM3939882 KrasG12D_D0_R1_ATAC-seq
GSM3939883 KrasG12D_D0_R2_ATAC-seq
GSM3939884 KrasG12D_D2_R1_ATAC-seq
This SubSeries is part of SuperSeries:
GSE134236 Mutant Kras co-opts a progenitor-derived enhancer network to initiate pancreatic tumorigenesis
Relations
BioProject PRJNA554362
SRA SRP214495

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Supplementary file Size Download File type/resource
GSE134230_RAW.tar 1.5 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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