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Series GSE211165 Query DataSets for GSE211165
Status Public on Jun 08, 2023
Title KDM6A Epigenetically Regulates Subtype Plasticity in Small Cell Lung Cancer
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Using a CRISPR-based autochthonous SCLC GEMM to study the consequences of KDM6A/UTX inactivation, we found that KDM6A inactivation induced plasticity from ASCL1 to NEUROD1 resulting in SCLC tumors with open chromatin at the NEUROD1 promoter that express both ASCL1 and NEUROD1. Mechanistically, KDM6A binds and maintains ASCL1 target genes in an active chromatin state with its loss increasing H3K27me3 near their promoters leading to a cell state that is primed for ASCL1 to NEUROD1 subtype switching. This work identifies KDM6A as an epigenetic regulator that controls ASCL1 to NEUROD1 subtype plasticity and provides a novel autochthonous SCLC GEMM to model ASCL1 and NEUROD1 subtype heterogeneity and plasticity, which is found in 35-40% of human SCLCs.
 
Overall design Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone marks H3K4me2 and H3K27me3 and the histone demethylase KDM6A in primary mouse small cell lung cancer cells (SCLC) derived from SCLC genetically-engineered mouse models that are KDM6A WT (sgControl RPP) or KDM6A-Mutant (sgKdm6a RPP).
 
Contributor(s) Duplaquet L, Oser MG
Citation(s) 37591951
Submission date Aug 12, 2022
Last update date Sep 08, 2023
Contact name Matthew Oser
Organization name Dana Farber Cancer Institute
Department Thoracic Oncology
Street address 360 Longwood Avenue
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (24)
GSM6454703 H3K27me3_sgCTRL_159-1
GSM6454704 H3K27me3_sgCTRL_1014
GSM6454705 H3K27me3_sgKDM6A_236L
This SubSeries is part of SuperSeries:
GSE228347 KDM6A Epigenetically Regulates Subtype Plasticity in Small Cell Lung Cancer
Relations
BioProject PRJNA869124

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Supplementary file Size Download File type/resource
GSE211165_RAW.tar 13.0 Gb (http)(custom) TAR (of BROADPEAK, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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