Chromatin-remodelling factor BRG1 selectively activates a subset of interferon-alpha-inducible genes

Nat Cell Biol. 2002 Oct;4(10):774-81. doi: 10.1038/ncb855.

Abstract

Brahma-related gene 1 (BRG1 ) is a key component of the ATP-dependent chromatin-remodelling SWI2-SNF2 complex and has been implicated in regulating gene expression, cell-cycle control and tumorigenesis. Here we report that BRG1 interacts with signal transducer and activator of transcription 2 (STAT2) - a transcription factor that regulates gene expression mediated by interferon-alpha (IFN-alpha). BRG1 enhances the IFN-alpha-induced expression of 9-27 and IFI27 but not that of four other target genes tested, showing that the activation of different target genes by STAT2 may involve alternative chromatin modifiers. Our results also suggest that the recruitment and activation of BRG1 may require other cis-acting and trans-acting elements in addition to STAT2. Our study links the SWI2-SNF2 complex to the regulation of cytokine-induced gene expression and may identify a molecular mechanism of BRG1-mediated gene activation and tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Cell Nucleus / drug effects
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Transformation, Neoplastic / genetics
  • Chromatin / drug effects
  • Chromatin / genetics*
  • DNA Helicases
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / drug effects
  • Eukaryotic Cells / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • HeLa Cells
  • Humans
  • Interferon-alpha / genetics*
  • Interferon-alpha / metabolism
  • Interferon-alpha / pharmacology
  • Mutation / drug effects
  • Mutation / genetics
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Structure, Tertiary / drug effects
  • Protein Structure, Tertiary / genetics
  • STAT2 Transcription Factor
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Interferon-alpha
  • Nuclear Proteins
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • Trans-Activators
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases