Lookup NU author(s): Dr Martina Finetti, Dr Daniel Williamson
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 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.
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
Altmetrics provided by Altmetric
