The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene

Biochem Biophys Res Commun. 2020 Apr 30;525(2):477-482. doi: 10.1016/j.bbrc.2020.02.101. Epub 2020 Feb 25.


Plasmacytoid dendritic cells (pDCs) are characterized by an exclusive expression of nucleic acid sensing Toll-like receptor 7 (TLR7) and TLR9, and production of high amounts of type I interferon (IFN) in response to TLR7/9 signaling. This function is crucial for both antiviral immunity and the pathogenesis of autoimmune diseases. An Ets family transcription factor, i.e., Spi-B (which is highly expressed in pDCs) is required for TLR7/9 signal-induced type I IFN production and can transactivate IFN-α promoter in synergy with IFN regulatory factor-7 (IRF-7). Herein, we analyzed how Spi-B contributes to the transactivation of the Ifna4 promoter. We performed deletion and/or mutational analyses of the Ifna4 promoter and an electrophoretic mobility shift assay (EMSA) and observed an Spi-B binding site in close proximity to the IRF-7 binding site. The EMSA results also showed that the binding of Spi-B to the double-stranded DNA probe potentiated the recruitment of IRF-7 to its binding site. We also observed that the association of Spi-B with transcriptional coactivator p300 was required for the Spi-B-induced synergistic enhancement of the Ifna4 promoter activity by Spi-B. These results clarify the molecular mechanism of action of Spi-B in the transcriptional activation of the Ifna4 promoter.

Keywords: IRF-7; Interferon-α; Plasmacytoid dendritic cell; Spi-B; p300.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • E1A-Associated p300 Protein / metabolism
  • HEK293 Cells
  • Humans
  • Interferon-alpha / genetics*
  • Mice
  • Mutation
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / metabolism*
  • Transcriptional Activation*


  • Interferon-alpha
  • Proto-Oncogene Proteins c-ets
  • Spi-B protein, mouse
  • E1A-Associated p300 Protein
  • EP300 protein, human