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Series GSE129380 Query DataSets for GSE129380
Status Public on Sep 28, 2019
Title An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer [ChIP-Seq]
Organisms Sarcophilus harrisii; Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Loss of MHC class I (MHC-I) antigen presentation in cancer cells can lead to immunotherapy resistance. Using a genome-wide CRISPR/Cas9 screen we identify a critical role for polycomb repressive complex 2 (PRC2) in the coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP). This evolutionarily conserved function of PRC2 promotes evasion of T-cell mediated immunity, enabling tumor transmission to non-histocompatible recipients in small cell lung cancer (SCLC) and Tasmanian Devil Facial Tumor. MHC-I APP gene promoters in MHC-I low cancers harbour bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine induced MHC-I APP gene upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological silencing of MHC-I expression highlights a conserved mechanism by which cancers arising from these primitive tissues coopt PRC2 activity to enable immune evasion.
 
Overall design Changes in histone modifications and IRF1 binding with EZH2 inhibitor in mouse SCLC and human K562 cells
 
Contributor(s) Burr ML, Dawson MA, Lam E
Citation(s) 31564637
Submission date Apr 05, 2019
Last update date Dec 10, 2019
Contact name Mark Dawson
E-mail(s) mark.dawson@petermac.org
Organization name Peter MacCallum Cancer Centre
Street address 305 Grattan Street
City Melbourne
State/province VIC
ZIP/Postal code 3000
Country Australia
 
Platforms (3)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL26397 Illumina NextSeq 500 (Sarcophilus harrisii)
Samples (24)
GSM3712085 RP116-H3K27me3_ChIP_Control
GSM3712086 RP116-H3K27me3_ChIP_EPZ
GSM3712087 RP116-H3K4me3_ChIP_Control
This SubSeries is part of SuperSeries:
GSE129382 An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer
Relations
BioProject PRJNA531105
SRA SRP191040

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Supplementary file Size Download File type/resource
GSE129380_RAW.tar 12.8 Mb (http)(custom) TAR (of BROADPEAK, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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