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

Cancer Cell. 2019 Jan 14;35(1):95-110.e8. doi: 10.1016/j.ccell.2018.11.014. Epub 2018 Dec 27.


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.

Keywords: EZH2; SMARCA4; SMARCB1; atypical teratoid rhabdoid tumor; chromatin states; pediatric brain tumor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • SMARCB1 Protein / metabolism*
  • Sequence Analysis, DNA
  • Survival Analysis
  • Teratoma / metabolism*


  • Chromatin
  • Histones
  • Polycomb-Group Proteins
  • RE1-silencing transcription factor
  • Repressor Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human

Supplementary concepts

  • Teratoid Tumor, Atypical