Transcriptional control of the TNF gene.
Transcriptional control of the TNF gene.
复制标题
DOI：
10.1159/000289196
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Goldfeld AE
中科院分区：
文献类型：
--
作者：
Falvo JV;Tsytsykova AV;Goldfeld AE
细胞因子TNF是免疫和炎症反应的重要介质。TNF基因是一种即时早期基因，在暴露于广泛的病原体和炎症和应激信号后，在各种细胞类型中迅速转录。TNF基因表达在转录水平上的调控是细胞类型和刺激特异性的，涉及将不同的转录因子集合募集到紧凑和模块化的启动子区域。在这篇综述中，我们描述了我们目前对多种细胞类型（包括T细胞、B细胞、巨噬细胞、肥大细胞、树突状细胞和成纤维细胞）中各种细胞外刺激特异性激活TNF转录的机制的理解。我们讨论了活化T细胞的核因子和其他转录因子和共激活因子在增强体形成中的作用，以及核因子κB作为TNF基因经典激活因子的作用的矛盾证据。我们描述了进化上保守的顺式调控DNA基序在TNF位点对TNF基因转录的影响，与单核苷酸多态性的中性效应形成对比。我们还评估了染色质组织，表观遗传修饰和肿瘤坏死因子位点的远程染色体相互作用的调节作用。
The cytokine TNF is a critical mediator of immune and inflammatory responses. The TNF gene is an immediate early gene, rapidly transcribed in a variety of cell types following exposure to a broad range of pathogens and signals of inflammation and stress. Regulation of TNF gene expression at the transcriptional level is cell type- and stimulus-specific, involving the recruitment of distinct sets of transcription factors to a compact and modular promoter region. In this review, we describe our current understanding of the mechanisms through which TNF transcription is specifically activated by a variety of extracellular stimuli in multiple cell types, including T cells, B cells, macrophages, mast cells, dendritic cells, and fibroblasts. We discuss the role of nuclear factor of activated T cells and other transcription factors and coactivators in enhanceosome formation, as well as the contradictory evidence for a role for nuclear factor κB as a classical activator of the TNF gene. We describe the impact of evolutionarily conserved cis-regulatory DNA motifs in the TNF locus upon TNF gene transcription, in contrast to the neutral effect of single nucleotide polymorphisms. We also assess the regulatory role of chromatin organization, epigenetic modifications, and long-range chromosomal interactions at the TNF locus.