Critical Role of Transcription Factor PU.1 in the Function of the OX40L/TNFSF4 Promoter in Dendritic Cells.
Critical Role of Transcription Factor PU.1 in the Function of the OX40L/TNFSF4 Promoter in Dendritic Cells.
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DOI：
10.1038/srep34825
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发表时间：
2016-10-06
影响因子：
4.6
通讯作者：
Nishiyama C
中科院分区：
文献类型：
--
作者：
Yashiro T;Hara M;Ogawa H;Okumura K;Nishiyama C
PU.1是一种属于Ets家族的造血谱系特异性转录因子。我们研究了PU.1在树突状细胞（dc）中OX40L表达中的作用，因为OX40L的细胞类型特异性表达的调节机制主要局限于抗原呈递细胞，尽管它在Th2和Tfh发育中起关键作用，但在很大程度上是未知的。PU.1敲低可降低小鼠dc中OX40L的表达。染色质免疫沉淀（ChIP）实验表明，PU.1组成性地结合到OX40L启动子的近端区域。报告基因分析和电泳迁移率转移分析显示，PU.1通过直接结合最近端的Ets基序来反激活OX40L启动子。我们发现这个Ets基序在小鼠和人类之间是保守的，并且在使用人类单核细胞来源的dc的ChIP实验中，PU.1与人类OX40L启动子结合。基于ChIP-seq数据集的ChIP分析显示，在小鼠dc中，PU.1除了与OX40L基因转录起始位点最近的位点结合外，还结合了远离OX40L基因转录起始位点的几个位点。本研究确定了PU.1调控的OX40L启动子的结构。这也表明PU.1通过基因上的多个结合位点参与了小鼠OX40L的表达。
PU.1 is a hematopoietic lineage-specific transcription factor belonging to the Ets family. We investigated the role of PU.1 in the expression of OX40L in dendritic cells (DCs), because the regulatory mechanism of cell type-specific expression of OX40L, which is mainly restricted to antigen-presenting cells, is largely unknown despite the critical involvement in Th2 and Tfh development. PU.1 knockdown decreased the expression of OX40L in mouse DCs. Chromatin immunoprecipitation (ChIP) assays demonstrated that PU.1 constitutively bound to the proximal region of the OX40L promoter. Reporter assays and electrophoretic mobility shift assays revealed that PU.1 transactivated the OX40L promoter through direct binding to the most-proximal Ets motif. We found that this Ets motif is conserved between mouse and human, and that PU.1 bound to the human OX40L promoter in ChIP assay using human monocyte-derived DCs. ChIP assays based on ChIP-seq datasets revealed that PU.1 binds to several sites distant from the transcription start site on the OX40L gene in addition to the most-proximal site in mouse DCs. In the present study, the structure of the OX40L promoter regulated by PU.1 is determined. It is also suggested that PU.1 is involved in mouse OX40L expression via multiple binding sites on the gene.
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
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DOI：
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发表时间：
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作者：
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