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| Status |
Public on May 24, 2024 |
| Title |
Enhanced Phase Separation Mediated Oncogenicity [ChIP-Seq experiment] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Chromosome translocation is known to generate oncogenes such as SS18-SSX1, but the underlying mechanism remains unknown. Here we show that enhanced phase separation acquired by translocation mediates oncogenic transformation. SSX fusion dramatically enhances the phase separation property of SS18 protein through H2AK119ub. Super condensates generated by SS18-SSX recruit acetyltransferases CBP/P300 as wild type SS18, but exclude HDACs such that H3K27ac accumulates abnormally at loci from those normally occupied by SS18, resulting aberrant silencing and activation of target genes. Consistently, we show that inhibition of H3K27ac can attenuate the tumorigenicity of the fusion oncoprotein. These results provide the first case for phase separation as a transforming event to generate oncogene and super phase separation can be targeted for cancer therapy.
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| Overall design |
We analyzed the H3K27me3, PRC1/2 and cohesin-CTCF occupancy during synovial sarcomagenesis triggered by SS18-SSX1 overexpression and the H2AK119ub in IMR90 cell line.
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| Contributor(s) |
Kuang J, Pei D |
| Citation(s) |
38678233 |
| |
| Submission date |
Apr 08, 2024 |
| Last update date |
May 24, 2024 |
| Contact name |
kuang junqi |
| E-mail(s) |
kuangjunqi@westlake.edu.cn
|
| Organization name |
westlake University
|
| Street address |
No.18 Shilongshan Road
|
| City |
hangzhou |
| ZIP/Postal code |
310024 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA1097529 |
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