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Enhanced Phase Separation Mediated Oncogenicity [ChIP-Seq]

GSE211454 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2024/05/24 Platform GPL24676
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 (we do not have the data in your figures?). 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.
Published in
Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates
Kuang J, Li P, Zhai Z et al. · Molecular cancer 2024 · PMID 38678233 · doi:10.1186/s12943-024-02002-1
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Also filed as BioProject PRJNA870444 and SRA study SRP392681. Searching any of these in the dataset finder brings you back here.

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