|
| Status |
Public on Apr 14, 2023 |
| Title |
BAZ2A-RNA dependent association with TOP2A and KDM1A represses gene expression in prostate cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
BAZ2A represses rRNA genes (rDNA) that are transcribed by RNA polymerase I. In prostate cancer (PCa), BAZ2A function goes beyond this role because it represses genes frequently silenced in metastatic disease. However, the mechanisms of this BAZ2A-mediated repression remain elusive. Here, we show that BAZ2A represses genes through its RNA-binding TAM domain using mechanisms differing from rDNA silencing. Although the TAM domain mediates BAZ2A recruitment to rDNA, in PCa, this is not required for BAZ2A association with target genes. Instead, the BAZ2A-TAM domain in association with RNA mediates the interaction with topoisomerase 2A (TOP2A) and histone demethylase KDM1A, whose expression positively correlates with BAZ2A levels in localized and metastatic PCa. TOP2A and KDM1A pharmacological inhibition up-regulate BAZ2A-repressed genes that are regulated by inactive enhancers bound by BAZ2A, whereas rRNA genes are not affected. Our findings showed a novel RNA-based mechanism of gene regulation in PCa. Furthermore, we determined that RNA-mediated interactions between BAZ2A and TOP2A and KDM1A repress genes critical to PCa and may prove to be useful to stratify prostate cancer risk and treatment in patients.
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| |
|
| Overall design |
RNA seq in human PC3 cells
|
| Web link |
https://www.life-science-alliance.org/content/lsa/6/7/e202301950.full.pdf
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| |
|
| Contributor(s) |
Roganowicz M, Bär D, Bersaglieri C, Aprigliano R, Santoro R |
| Citation(s) |
37184661 |
| Submission date |
Jul 08, 2021 |
| Last update date |
Jul 14, 2023 |
| Contact name |
Raffaella Santoro |
| E-mail(s) |
raffaella.santoro@dmmd.uzh.ch
|
| Phone |
+41 44 635 54 75
|
| Organization name |
University of Zurich
|
| Department |
Dep. of Molecular Mechanisms of Disease
|
| Street address |
Winterthurerstrasse 190
|
| City |
Zurich |
| ZIP/Postal code |
8057 |
| Country |
Switzerland |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (15)
|
|
| Relations |
| BioProject |
PRJNA744891 |
| SRA |
SRP327515 |
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