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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

Lookup NU author(s): Dr Martina Finetti, Dr Daniel Williamson

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Abstract

© 2018 Elsevier Inc. 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. © 2018 Elsevier Inc. Erkek et al. show that in atypical teratoid rhabdoid tumors (ATRT), which often lack the SWI/SNF complex component SMARCB1, a large fraction of SMARCB1 binding loci in normal brain is bound by EZH2 but without H3K27me3 and remains in an active state, and some of these genes are essential for ATRT survival.

Publication metadata

Author(s): Erkek S, Johann PD, Finetti MA, Drosos Y, Chou H-C, Zapatka M, Sturm D, Jones DTW, Korshunov A, Rhyzova M, Wolf S, Mallm J-P, Beck K, Witt O, Kulozik AE, Fruhwald MC, Northcott PA, Korbel JO, Lichter P, Eils R, Gajjar A, Roberts CWM, Williamson D, Hasselblatt M, Chavez L, Pfister SM, Kool M

Publication type: Article

Publication status: Published

Journal: Cancer Cell

Year: 2019

Volume: 35

Issue: 1

Pages: 95-110.e8

Print publication date: 14/01/2019

Online publication date: 27/12/2018

Acceptance date: 21/11/2018

Date deposited: 07/02/2019

ISSN (print): 1535-6108

ISSN (electronic): 1878-3686

Publisher: Cell Press

URL: https://doi.org/10.1016/j.ccell.2018.11.014

DOI: 10.1016/j.ccell.2018.11.014

PubMed id: 30595504

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