Communication between NF-κB and Sp1 controls histone acetylation within the proximal promoter of the monocyte chemoattractant protein 1 gene
Communication between NF-κB and Sp1 controls histone acetylation within the proximal promoter of the monocyte chemoattractant protein 1 gene
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DOI：
10.4049/jimmunol.170.8.4139
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发表时间：
2003-04-15
影响因子：
4.4
通讯作者：
Boss, JM
中科院分区：
文献类型：
--
作者：
Boekhoudt, GH;Guo, Z;Boss, JM
TNF对单核细胞趋化蛋白I基因（MCP-1）的诱导通过一个NF-κ B依赖性远端调控区和一个Sp1依赖性近端调控区发生，这两个调控区之间相隔2.2 kb的序列。为了研究这些区域如何协调MCP-1对TNF的激活，进行了实验以检查辅激活因子的作用、局部染色质结构的变化以及MCP-1调节区域组蛋白的乙酰化。发现E1 a敏感的辅激活因子是表达所需的。体内核酸酶敏感性测定确定了近端和远端区域对TNF应答的变化，这些变化依赖于NF-κ B和Sp1的p65亚基。染色质免疫沉淀用于分析因子组装和组蛋白乙酰化在远端和近端区域显示，Sp1结合和组蛋白。近端区域的乙酰化依赖于NF-κ B p65。相反，Sp1组装在近端区域所需的p65结合和乙酰化的远端区域，这表明在基因激活过程中的两个区域之间的通信。这些数据和中间区域序列的NF-κ B p65依赖性组蛋白乙酰化表明MCP-1调节区响应TNF的组装、乙酰化和可及性的潜在顺序。
The induction of the monocyte chemoattractant protein I gene (MCP-1) by TNF occurs through an NF-kappaB-dependent distal regulatory region and an Sp1-dependent proximal regulatory region that are separated by 2.2 kb of sequence. To investigate how these regions coordinate activation of MCP-1 in response to TNF, experiments were performed to examine the role of coactivators, changes in local chromatin structure, and the acetylation of histones at the MCP-1 regulatory regions. An E1a-sensitive coactivator was found to be required for expression. In vivo nuclease sensitivity assays identified changes in response to TNF at both the proximal and distal regions that were dependent on the p65 subunit of NF-kappaB and Sp1. Chromatin immunoprecipitations used to analyze factor assembly and histone acetylation at the distal and proximal regions showed that Sp1 binding to and histone. acetylation of the proximal region was dependent on NF-kappaB p65. Conversely, Sp1 assembly at the proximal region was required for p65 binding to and acetylation of the distal region, suggesting communication between the two regions during gene activation. These data and the NF-kappaB p65-dependent histone acetylation of a middle region sequence suggest a potential order for the assembly, acetylation and accessibility of the MCP-1 regulatory regions in response to TNF.