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| Status |
Public on Mar 13, 2023 |
| Title |
Dissecting the interface between ARID1A and mRNA translation in bladder cancer (CUT&Tag) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Chromatin remodeling and protein synthesis are tightly regulated processes that impact gene expression and cellular phenotypes. However, it is unknown if these two regulatory mechanisms are linked or exert independent effects in normal epithelial physiology and disease states. We have uncovered a new functional relationship between the chromatin remodeler ARID1A and mRNA translation elongation that is involved in maintaining cellular fitness in the context of bladder carcinogenesis. Loss of ARID1A triggers inhibition of the translation elongation factor eEF2 and ribosome accumulation, which results in a reduction in protein synthesis. In the setting of ARID1A deficiency the bladder carcinogen BBN induces DNA damage and cell death without impacting cancer initiation. As such, ARID1A is necessary for tumorigenesis. Remarkably, restoration of translation elongation through eEF2 is sufficient to initiate transformation in the context of ARID1A loss. However, dependence on ARID1A for transformation appears to be context specific, as loss of ARID1A after tumor establishment is sufficient for cancer progression.
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| |
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| Overall design |
CUT&Tag data from 3 biological replicates each for wild-type (WT) and ARID1A knockout (KO) cells
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| |
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| Contributor(s) |
Jana S, Brahma S, Arora S, Hsieh AC |
| Citation(s) |
37084735 |
| |
| Submission date |
Apr 21, 2022 |
| Last update date |
Jun 20, 2023 |
| Contact name |
Sonali Arora |
| E-mail(s) |
sarora@fredhutch.org
|
| Organization name |
FHCRC
|
| Street address |
1100 Fairview Ave N,
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL30172 |
NextSeq 2000 (Mus musculus) |
|
| Samples (19)
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| This SubSeries is part of SuperSeries: |
| GSE201222 |
Dissecting the interface between ARID1A and mRNA translation in bladder cancer |
|
| Relations |
| BioProject |
PRJNA830456 |
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