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| Status |
Public on May 02, 2019 |
| Title |
Genome-wde mapping of BRD9 binding sites and gene expression changes upon BRD9 knockdown |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Leukemia is characterized by genetic and epigenetic mutations resulting in selection of cancer cells, which are unable to differentiate. While genetic alterations are difficult to target, the epigenome is intrinsically dynamic and readily offers new therapeutic strategies. Thus, identifying cancer-specific context-dependent targets and unraveling their biological function may open up new therapeutic perspectives. Here, we identify bromodomain-containing protein 9 (BRD9) as a critical target required in acute myeloid leukemia (AML). We show that BRD9 is overexpressed in AML cells including ex vivo primary blasts compared to CD34+ cells. By targeting BRD9 expression in AML, we observed an alteration in proliferation and survival, ultimately resulting in the induction of apoptosis. Intriguingly, genome-wide profiling revealed that BRD9 binds enhancer regions in a cell type-specific manner, regulating cell type-related processes. We unveil a novel BRD9-sustained STAT5 pathway activation via regulation of SOCS3 expression levels. Our findings identify a previously undescribed BRD9-STAT5 axis as critical for leukemia maintenance, suggesting BRD9 as a potential therapeutic target.
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| |
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| Overall design |
Mapping BRD9 binding sites in U937 and HeLa cells, and examine expression changes upon shBRD9 in U937 cells
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| |
|
| Contributor(s) |
Del Gaudio N, Liu NQ, Altucci L |
| Citation(s) |
31000698 |
| |
| Submission date |
Apr 07, 2019 |
| Last update date |
Nov 11, 2022 |
| Contact name |
Ning Qing Liu |
| E-mail(s) |
n.liu@erasmusmc.nl
|
| Organization name |
Erasmus University Medical Center Rotterdam
|
| Department |
Hematology
|
| Street address |
Wytemaweg 80
|
| City |
Rotterdam |
| ZIP/Postal code |
3015 CN |
| Country |
Netherlands |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (6)
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|
| Relations |
| BioProject |
PRJNA531322 |
| SRA |
SRP191312 |
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