Activation of β-catenin/TCF targets following loss of the tumor suppressor SNF5

Oncogene. 2014 Feb 13;33(7):933-8. doi: 10.1038/onc.2013.37. Epub 2013 Feb 25.


The SWI/SNF chromatin remodeling complex is a master regulator of developmental cell-fate decisions, although the key target pathways are poorly characterized. Here, we interrogated the contribution of the SWI/SNF subunit and tumor suppressor SNF5 to the regulation of developmental pathways using conditional mouse and cell culture models. We find that loss of SNF5 phenocopies β-catenin hyperactivation and that SNF5 is essential for regulating Wnt/β-catenin pathway target expression. These data provide insight into chromatin-based mechanisms that underlie developmental regulation and elucidate the emerging theme that mutation of this tumor suppressor complex can activate developmental pathways by uncoupling them from upstream control.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Chromosomal Proteins, Non-Histone / deficiency
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • Medulloblastoma / genetics
  • Mice
  • Mice, Transgenic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Rhabdoid Tumor
  • SMARCB1 Protein
  • Transcription Factor 4
  • Transcription Factors / deficiency
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptome
  • Tumor Cells, Cultured
  • Wnt Signaling Pathway*


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • RNA, Messenger
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors