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

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/29000
Title
The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene
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Description

Abstract

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

(医博甲750)

Author
著者 宮嵜 亮
著者(ヨミ) ミヤザキ リョウ
著者(別表記) Miyazaki Ryo
Publication Title
Biochemical and biophysical research communications
Publication Title Alternative
Biochem Biophys Res Commun.
Volume
525
Issue
4
Start Page
477
End Page
482
Publisher
Academic Press
Elsevier
Published Date
2020-04-30
ISSN
0006-291X
NCID
AA00564395
PMID
32111355
DOI
10.1016/j.bbrc.2020.02.101
Resource Type
Thesis or Dissertation
Language
eng
Rights
Copyright © 2020 Elsevier Inc.
"This is the Publisher's Version of the following article: The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene; Biochemical and biophysical research communications; Volume 525 Issue 2 (2020) Pages:477-482; doi: 10.1016/j.bbrc.2020.02.101, which has been published in final form at https://doi.org/10.1016/j.bbrc.2020.02.101 . "
この博士論文の本文については、次のエルゼビアの著作権ポリシーの規定により公開しています。「博士論文の場合は、エンバーゴ期間に関係なく機関リポジトリに出版社版を公開することができます。」 The text of this doctoral dissertation is published according to the following Elsevier copyright policy. "In the case of doctoral dissertations, publishers can be published in institutional repositories regardless of the Embargo period."
Text Version
ETD
Grant ID
博甲第750号
Grant Date
2020-06-25
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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