TNF regulates the in vivo occupancy of both distal and proximal regulatory regions of the MCP-1/JE gene
TNF regulates the in vivo occupancy of both distal and proximal regulatory regions of the MCP-1/JE gene
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DOI：
10.1016/s1074-7613(00)80412-4
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发表时间：
1996-05-01
期刊：
影响因子：
32.4
通讯作者：
Boss, JM
中科院分区：
文献类型：
--
作者：
Ping, DS;Jones, PL;Boss, JM
体内基因组足迹法（IVGF）被用来检查在TNF激活小鼠炎症反应基因MCP-1/JE过程中的调节位点占有率。响应于TNF，启动子远端和近端调控区在体内被占据。EMSA分析表明，虽然一些参与表达的因子，包括NF-κ B，在TNF处理后易位到细胞核，但其他因子已经存在并能够在体外结合DNA。蛋白激酶抑制剂的研究表明，蛋白磷酸化所需的TNF活化，但不是因子组装。这些研究为TNF介导的基因调控的多步骤模型提供了证据，该模型涉及染色质可及性、转录因子复合物组装和蛋白质磷酸化。
In vivo genomic footprinting (IVGF) was used to examine regulatory site occupancy during the activation of the murine inflammatory response gene MCP-1/JE by TNF. In response to TNF, both promoter distal and proximal regulatory regions became occupied in vivo. EMSA analysis showed that while some of the factors involved in expression, including NF-kappa B, were translocated to the nucleus following TNF treatment, others were already present and able to bind DNA in vitro. Protein kinase inhibitor studies showed that protein phosphorylation was required for TNF activation but not factor assembly. These studies provide evidence for a multistep model of TNF-mediated gene regulation involving chromatin accessibility, transcription factor complex assembly, and protein phosphorylation.