Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation

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 EilsAmar Gajjar, Charles W.M. Roberts, Daniel Williamson, Martin Hasselblatt, Lukas Chavez, Stefan M. Pfister, Marcel Kool

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

64 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)95-110.e8
TijdschriftCancer Cell
Volume35
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 14 jan. 2019
Extern gepubliceerdJa

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