Transcription Factors Oct-1 and GATA-3 Cooperatively Regulate Th2 Cytokine Gene Expression via the RHS5 within the Th2 Locus Control Region.
Transcription Factors Oct-1 and GATA-3 Cooperatively Regulate Th2 Cytokine Gene Expression via the RHS5 within the Th2 Locus Control Region.
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DOI：
10.1371/journal.pone.0148576
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Lee GR
中科院分区：
文献类型：
--
作者：
Kim K;Kim N;Lee GR
辅助性T细胞2型（Th 2）基因座控制区（LCR）调节Th 2细胞分化。几种转录因子结合LCR来调节Th 2细胞因子基因的表达，但Th 2细胞因子基因调控背后的分子机制尚不完全清楚。在这里，我们使用数据库分析和寡核苷酸竞争/电泳迁移率变动测定来寻找与RHS 5（Th 2 LCR内的DNA酶I超敏位点（DHS））结合的转录因子。因此，我们证明了GATA结合蛋白3（加塔-3）、E26转化特异性蛋白1（Ets-1）、八聚体转录因子1（Oct-1）和Oct-2选择性地与RHS 5结合。此外，染色质免疫沉淀和荧光素酶报告基因测定显示，Oct-1和Oct-2结合在IL 4启动子区域和Th 2 LCR内，并且Oct-1和加塔-3或Oct-2通过RHS 5协同触发IL 4启动子的反式激活活性。这些结果表明Oct-1和加塔-3/Oct-2以协同方式指导Th 2细胞因子基因表达。
The T helper type 2 (Th2) locus control region (LCR) regulates Th2 cell differentiation. Several transcription factors bind to the LCR to modulate the expression of Th2 cytokine genes, but the molecular mechanisms behind Th2 cytokine gene regulation are incompletely understood. Here, we used database analysis and an oligonucleotide competition/electrophoretic mobility shift assays to search for transcription factors binding to RHS5, a DNase I hypersensitive site (DHS) within the Th2 LCR. Consequently, we demonstrated that GATA-binding protein-3 (GATA-3), E26 transformation-specific protein 1 (Ets-1), octamer transcription factor-1 (Oct-1), and Oct-2 selectively associate with RHS5. Furthermore, chromatin immunoprecipitation and luciferase reporter assays showed that Oct-1 and Oct-2 bound within the Il4 promoter region and the Th2 LCR, and that Oct-1 and GATA-3 or Oct-2 synergistically triggered the transactivational activity of the Il4 promoter through RHS5. These results suggest that Oct-1 and GATA-3/Oct-2 direct Th2 cytokine gene expression in a cooperative manner.