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PU.1 regulates Ccr7 gene expression by binding to its promoter in naïve CD4+ T cells.
FEBS Open Bio ( IF 2.6 ) Pub Date : 2020-04-30 , DOI: 10.1002/2211-5463.12861
Takuya Yashiro 1 , Hiromi Takeuchi 1 , Kazumi Kasakura 1 , Chiharu Nishiyama 1
Affiliation  

C‐C chemokine receptor type 7 (CCR7) is expressed on naïve T cells, B cells, and activated dendritic cells (DCs). We previously demonstrated that the transcription factor PU.1/Spi1 positively regulates the expression of CCR7 in DCs. In the present study, we investigated the role of PU.1 in CCR7 expression in T cells. To confirm whether PU.1 is involved in the expression of CCR7, we conducted a ChIP assay in various T cells purified from splenocytes and thymocytes and found that PU.1 binds to the Ccr7 promoter‐proximal region in spleen naïve CD4+ T cells, but not in thymocytes. Small interfering RNA‐mediated PU.1 knockdown resulted in decreased CCR7 expression in spleen naïve CD4+ T cells. Compared to naïve CD4+ T cells, Spi1 and Ccr7 mRNA levels decreased in Th1 and Th2 cells, in which PU.1 did not bind to the Ccr7 promoter, suggesting that CCR7 expression decreases due to the dissociation of PU.1 from the Ccr7 promoter during the development of effector T cells from naïve T cells. Collectively, we concluded that CCR7 expression level correlates with the binding level of PU.1 to the Ccr7 promoter and PU.1 acts as a transcriptional activator of the Ccr7 gene in naïve CD4+ T cells.

中文翻译:

PU.1通过结合其CD4 + T细胞中的启动子来调节Ccr7基因的表达。

C型趋化因子受体7型(CCR7)在幼稚T细胞,B细胞和活化树突状细胞(DC)上表达。我们先前证明了转录因子PU.1 / Spi1正调控DC中CCR7的表达。在本研究中,我们调查了PU.1在T细胞中CCR7表达中的作用。为了确认PU.1是否参与CCR7的表达,我们在从脾细胞和胸腺细胞纯化的各种T细胞中进行了ChIP分析,发现PU.1结合至脾脏CD4 + T细胞中Ccr7启动子附近区域,但不是在胸腺细胞中。小干扰RNA介导的PU.1敲低导致未处理的脾脏CD4 + T细胞中CCR7表达降低。与单纯的CD4 +T细胞,Spi1Ccr7 mRNA水平在Th1和Th2细胞中下降,其中PU.1不与Ccr7启动子结合,这表明CCR7表达下降是由于在效应子发育过程中PU.1与Ccr7启动子解离了。来自原始T细胞的T细胞。总的来说,我们得出结论,CCR7的表达水平与PU.1与Ccr7启动子的结合水平相关,而PU.1则充当了原始CD4 + T细胞中Ccr7基因的转录激活因子。
更新日期:2020-04-30
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