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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.

Abstract
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.
AuthorsSerap 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, Marcel Kool
JournalCancer cell (Cancer Cell) Vol. 35 Issue 1 Pg. 95-110.e8 (01 14 2019) ISSN: 1878-3686 [Electronic] United States
PMID30595504 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Elsevier Inc. All rights reserved.
Chemical References
  • Chromatin
  • Histones
  • Polycomb-Group Proteins
  • RE1-silencing transcription factor
  • Repressor Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
Topics
  • Binding Sites
  • Brain (metabolism)
  • Cell Line, Tumor
  • Chromatin (metabolism)
  • Chromatin Immunoprecipitation
  • Epigenomics (methods)
  • Gene Expression Regulation, Neoplastic
  • Histones (metabolism)
  • Humans
  • Polycomb-Group Proteins (metabolism)
  • Repressor Proteins (metabolism)
  • Rhabdoid Tumor (metabolism)
  • SMARCB1 Protein (chemistry, metabolism)
  • Sequence Analysis, DNA
  • Survival Analysis
  • Teratoma (metabolism)

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