Transcriptional regulation of mouse L-selectin.

Transcriptional regulation of mouse L-selectin.
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DOI:
10.1016/j.bbagrm.2008.10.004
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发表时间:
2009-02
影响因子:
4.7
通讯作者:
Ley, Klaus
Ley, Klaus
中科院分区:
生物学2区
文献类型:
--
作者:
Dang, Xitong;Raffler, Nikolai A.;Ley, Klaus

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L-选择素介导高内皮微静脉中淋巴细胞的初始束缚和滚动。为了研究小鼠L-选择素的转录调控,我们克隆了小鼠sell的4.5kb 5 '侧翼序列。荧光素酶分析的系列5 '-缺失突变体表明,前285 bp是足以驱动高启动子活性在EL 4细胞,但不是在Sell阴性HeLa细胞,这表明该片段窝藏最小的小鼠sell启动子,并含有顺式元件的淋巴细胞特异性表达。定点突变和染色质免疫沉淀表明,Mzf 1,Klf 2,Sp1,Ets 1和Irf 1结合并激活小鼠sell启动子。这些转录因子在EL 4细胞中的过表达增加了sell mRNA的表达。通过siRNA沉默Sp1的表达显著降低了EL 4细胞中sell启动子的活性。我们的结论是,出售转录调控Mzf 1,Klf 2,Sp1,Ets 1,和Irf 1。
L-selectin mediates the initial tethering and rolling of lymphocytes in high endothelial venules. To study the transcriptional regulation of mouse L-selectin, we cloned 4.5 kb 5’-flanking sequences of the mouse sell. Luciferase analysis of serial 5’-deletion mutants showed that the first 285 bp was sufficient to drive high promoter activity in EL4 cells, but not in Sell-negative HeLa cells, suggesting that this fragment harbors the minimal mouse sell promoter and contains cis-elements for lymphocyte-specific expression. Site-directed mutagenesis and chromatin immunoprecipitation showed that Mzf1, Klf2, Sp1, Ets1, and Irf1 bind to and activate the mouse sell promoter. Over expression of these transcription factors in EL4 cells increased expression of sell mRNA. Silencing the expression of Sp1 by siRNA significantly decreased sell promoter activity in EL4 cells. We conclude that sell transcription is regulated by Mzf1, Klf2, Sp1, Ets1, and Irf1.
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