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Series GSE61190 Query DataSets for GSE61190
Status Public on Jan 15, 2016
Title Epigenomic profiling of Non-small-cell Lung Cancer (NSCLC) cells with or without Eed
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Polycomb repressive complexes (PRC) are frequently implicated in human cancer acting either as oncogenes or tumor suppressors. Here we show that PRC2 is a critical regulator of Kras-driven non-small-cell lung cancer (NSCLC) progression. Modulation of PRC2 by either Ezh2 overexpression or Eed deletion enhances Kras-driven adenomagenesis and inflammation, respectively. Eed-loss-driven inflammation leads to massive macrophage recruitment and marked decline in tissue function. Additional Trp53 inactivation activates a cell autonomous epithelial-to-mesenchymal transition (EMT) program leading to an invasive mucinous adenocarcinoma. A switch between methylated/acetylated chromatin underlies the tumor phenotypic evolution, prominently involving genes controlled by Hippo/Wnt-signaling. Our observations in the mouse models were conserved in human cells. Importantly, PRC2 inactivation results in context-dependent phenotypic alterations, with implications for its therapeutic application.
Overall design We generated ChIP-seq from primary Kras;p53 (KP) cells in culture with and without Eed (KPE) and from KP primary tumors generated by injection of NSCLC into the tail vein. Mice were sacrificed on the onset of shortness of breath. We generated genome-wide expression profiles (RNA-seq) and Nuclease Accessibility (NA)-seq in primary KP and KPE tumor cells. NA-seq was also performed in A549 cells.
Contributor(s) Gargiulo G, Serresi M, Cesaroni M, de Rink I
Citation(s) 26766588
Submission date Sep 08, 2014
Last update date May 15, 2019
Contact name Gaetano Gargiulo
Organization name Max Delbrüch Center
Department Molecular Oncology
Street address Robert-Rössle-Straße 10
City Berlin
ZIP/Postal code 13125
Country Germany
Platforms (3)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (31)
GSM1499208 2249_10_I59 Input sample rep1
GSM1499209 2249_7__60-K27me3 ChIP sample rep1
GSM1499210 2249_5__58-K27me3 ChIP sample rep2
BioProject PRJNA260490
SRA SRP046306

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Supplementary file Size Download File type/resource
GSE61190_RAW.tar 1.4 Gb (http)(custom) TAR (of BED, BIGWIG, BW)
GSE61190_readcounts.txt.gz 1.0 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file

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