Chromatin-remodelling factor BRG1 selectively activates a subset of interferon-alpha-inducible genes.
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.
Huang
Mei
M
Laboratory of Molecular and Developmental Immunology, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609.
Qian
Feng
F
Hu
Yuanyu
Y
Ang
Chengeng
C
Li
Zhong
Z
Wen
Zilong
Z
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002843:Chromatin / Q000187:drug effects / Q000235:genetics*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000235:genetics; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
D002843:Chromatin; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D009687:Nuclear Proteins; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases