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Enhanced Phase Separation Mediated Oncogenicity [HiC IMR-90]

ABSTRACT: Enhanced Phase Separation Mediated Oncogenicity [HiC IMR-90]

PROVIDER: PRJNA1097544 | ENA |

REPOSITORIES: ENA

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Enhanced Phase Separation Mediated Oncogenicity [HiC]

Project description:Enhanced Phase Separation Mediated Oncogenicity [HiC]

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Enhanced Phase Separation Mediated Oncogenicity [HiC IMR-90]

Project description: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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ChIP-seq from IMR-90 (ENCSR970FKL)

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ChIP-seq from IMR-90 (ENCSR664OKA)

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Sequencing of human IMR-90 at 27 and 55 population doublings

Project description:Comparisong of gene expression of human IMR-90 at 27 and 55 population doublings. RNA-seq data comprises 2 groups: 27 and 55 population doublings of IMR-90. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)

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microRNA-seq from IMR-90 (ENCSR123QKC)

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