| Literature DB >> 29502955 |
Ana Banito1, Xiang Li2, Aimée N Laporte3, Jae-Seok Roe4, Francisco Sanchez-Vega5, Chun-Hao Huang1, Amanda R Dancsok3, Katerina Hatzi1, Chi-Chao Chen2, Darjus F Tschaharganeh1, Rohit Chandwani5, Nilgun Tasdemir1, Kevin B Jones6, Mario R Capecchi7, Christopher R Vakoc4, Nikolaus Schultz5, Marc Ladanyi5, Torsten O Nielsen3, Scott W Lowe8.
Abstract
Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands. Via KDM2B, SS18-SSX1 binds and aberrantly activates expression of developmentally regulated genes otherwise targets of polycomb-mediated repression, which is restored upon KDM2B depletion, leading to irreversible mesenchymal differentiation. Thus, SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression.Entities:
Keywords: CRISPR/Cas9-mediated endogenous protein tagging; DNA methylation; SWI/SNF; epigenetics; non-canonical polycomb repressive complex; oncogenic gene fusion; sarcoma
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Year: 2018 PMID： 29502955 PMCID： PMC5881394 DOI： 10.1016/j.ccell.2018.01.018
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743