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| Status |
Public on Feb 02, 2017 |
| Title |
Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2 |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Adenosquamous lung tumors may result from cellular plasticity. We demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, included Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions.
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| Overall design |
We performed chromatin immunoprecipitation (ChIP) on microdissected tumors confirmed to be either ADC or SCC by histology and qPCR. The two activating marks, histone H3 lysine 4 tri-methylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac), and the PRC2 derived silencing mark, histone H3 lysine 27 tri-methylation (H3K27me3) were immunoprecipitated, followed by sequencing the chromatin bound DNA.
Examination of 3 different histone modifications in 2 histological subtypes of mouse tumors
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| Contributor(s) |
Watanabe H, Wong K |
| Citation(s) |
28387316 |
| |
| Submission date |
Feb 01, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Hideo Watanabe |
| E-mail(s) |
hideo.watanabe@mssm.edu
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine
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| Lab |
Hideo Watanabe
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| Street address |
One Gustave L. Levy Place
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA369478 |
| SRA |
SRP098678 |
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