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Comprehensive analysis of chromatin states in atypical teratoid/rhabdoid tumor identifies diverging roles for SWI/SNF and polycomb in gene regulation

Summary - Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation s...

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Main Authors: Erkek, Serap (Author) , Johann, Pascal-David (Author) , Zapatka, Marc (Author) , Sturm, Dominik (Author) , Jones, David T. W. (Author) , Korshunov, Andrey (Author) , Wolf, Stephan (Author) , Mallm, Jan-Philipp (Author) , Witt, Olaf (Author) , Kulozik, Andreas (Author) , Korbel, Jan Oliver (Author) , Lichter, Peter (Author) , Eils, Roland (Author) , Chavez, Lukas (Author) , Pfister, Stefan (Author) , Kool, Marcel (Author)
Other Authors: Northcott, Michael (Other)
Format: Article (Journal)
Language:English
Published: 2019
In: Cancer cell
Year: 2019, Volume: 35, Issue: 1, Pages: 95-110
ISSN:1878-3686
DOI:10.1016/j.ccell.2018.11.014
Online Access:Verlag, Volltext: https://doi.org/10.1016/j.ccell.2018.11.014
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S153561081830535X
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Author Notes:Serap Erkek, Pascal D. Johann, Martina A. Finetti, Yiannis Drosos, Hsien-Chao Chou, Marc Zapatka, Dominik Sturm, David T. W. Jones, Andrey Korshunov, Marina Rhyzova, Stephan Wolf, Jan-Philipp Mallm, Katja Beck, Olaf Witt, Andreas E. Kulozik, Michael C. Frühwald, Paul A. Northcott, Jan O. Korbel, Peter Lichter, Roland Eils, Amar Gajjar, Charles W. M. Roberts, Daniel Williamson, Martin Hasselblatt, Lukas Chavez, Stefan M. Pfister, and Marcel Kool
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Summary:Summary - Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation sequencing (ChIP-seq) on primary tumors for a series of active and repressive histone marks, we identified the chromatin states differentially represented in ATRTs compared with other brain tumors and non-neoplastic brain. Re-expression of SMARCB1 in ATRT cell lines enabled confirmation of our genome-wide findings for the chromatin states. Additional generation of ChIP-seq data for SWI/SNF and Polycomb group proteins and the transcriptional repressor protein REST determined differential dependencies of SWI/SNF and Polycomb complexes in regulation of diverse gene sets in ATRTs.
Item Description:Available online 27 December 2018
Gesehen am 08.05.2019
Physical Description:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2018.11.014

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