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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 09, 2023 |
| Title |
Small Cell Lung Cancer Subtype Plasticity is Regulated by KDM6A/UTX [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| 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 decreasing H3K4me1 and increasing H3K27me3 at enhancers of neuroendocrine genes 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.
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| Overall design |
ChIP-seq for Menin in a Kdm6a-WT mouse tumor derived cell lines (1014) CRISPR inactivated for KDM6A treated with VTP50469 or DMSO
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| Contributor(s) |
Olsen SN, Duplaquet L, Oser MG |
| Citation(s) |
37591951 |
| Submission date |
Mar 28, 2023 |
| Last update date |
Sep 08, 2023 |
| Contact name |
Leslie Duplaquet |
| E-mail(s) |
leslie_duplaquet@dfci.harvard.edu
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| Organization name |
DFCI
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| Department |
Medical Oncology
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| Lab |
Oser Lab
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| Street address |
360 Longwood Ave
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| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
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| Samples (8)
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| GSM7119226 |
INPUT, 1014 sgKdm6a, VTP, rep2 |
| GSM7119227 |
Menin-ChIP, 1014 sgKdm6a, DMSO, rep1 |
| GSM7119228 |
Menin-ChIP, 1014 sgKdm6a, DMSO, rep2 |
| GSM7119229 |
Menin-ChIP, 1014 sgKdm6a, VTP, rep1 |
| GSM7119230 |
Menin-ChIP, 1014 sgKdm6a, VTP, rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE228347 |
KDM6A Epigenetically Regulates Subtype Plasticity in Small Cell Lung Cancer |
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| Relations |
| BioProject |
PRJNA949517 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE228345_RAW.tar |
2.3 Gb |
(http)(custom) |
TAR (of TDF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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