The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene 転写因子Spi-BによるInterferon-α4遺伝子の転写活性化メカニズム
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著者
書誌事項
- タイトル
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The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene
- タイトル別名
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転写因子Spi-BによるInterferon-α4遺伝子の転写活性化メカニズム
- 著者名
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宮嵜, 亮
- 学位授与大学
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香川大学
- 取得学位
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博士(医学)
- 学位授与番号
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博甲第750号
- 学位授与年月日
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2020-06-25
注記・抄録
開始ページ : 477
終了ページ : 482
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.