 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 11, 2023 |
| Title |
The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes (ChIP-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Epigenetic regulators are frequently mutated in acute myeloid leukemia (AML). However, epigenetic dysregulation in AML extends beyond recurrently mutated factors and only little is known about the potential drivers in this context. Identification and characterization of novel epigenetic drivers impacting on AML biology will not only improve our basic understanding of AML but may also uncover novel options for therapeutic intervention.
To uncover novel epigenetic regulators in AML, we performed an in vivo short hairpin RNA (shRNA) screen in the context of CEBPA mutant AML. We identified the H3K4me2/3 demethylase KDM5C as a novel tumor suppressor in AML.
We found that lower Kdm5c/KDM5C expression levels are associated with accelerated growth of human and murine AML cell lines. In a CEBPA mutant AML mouse model, Kdm5c knockdown resulted in a more aggressive, immature and short-latency phenotype. Mechanistically, we show that knockdown of Kdm5c increased H3K4me3-levels globally. This translated into the up-regulation of a group of bivalently marked immature genes resulting in a de-differentiation phenotype which could be reversed by modulating levels of pro-differentiating factors. Finally, we could demonstrate that low levels of KDM5C was associated with a decrease in long-term disease-free survival, specifically in female patients. This emphasizes the clinical relevance of our findings and identifies KDM5C as a novel sex-specific tumor suppressor in AML.
|
| |
|
| Overall design |
ChIP-seq of H3K4me1, H3K4me3, H3K27me3, and H3K27ac in shControl versus shKdm5c Lp30 cells. ChIP-seqs were performed in biological duplicates.
|
| |
|
| Contributor(s) |
Trempenau ML, Schuster MB, Pundhir S, Kalviša A, Tapia M, Ge Y, Bagger FO, Shliaha P, Sroczynska P, Walfridsson J, Jensen ON, Helin K, Porse BT |
| Citation(s) |
36631623, 37794021 |
| Submission date |
Jul 06, 2020 |
| Last update date |
Oct 18, 2023 |
| Contact name |
Bo Porse |
| Organization name |
University of Copenhagen
|
| Department |
Finsen Laboratory and BRIC
|
| Lab |
Porse lab
|
| Street address |
Ole Maaløes Vej 5, 4
|
| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (16)
|
|
| This SubSeries is part of SuperSeries: |
| GSE141477 |
The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes |
|
| Relations |
| BioProject |
PRJNA644289 |
| SRA |
SRP270227 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE153821_RAW.tar |
1.4 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...