German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany.
Eur J Immunol. 2014 Jan;44(1):251-64. doi: 10.1002/eji.201243297. Epub 2013 Oct 9.
Tumor necrosis factor (TNF) is one of the key primary response genes in the immune system that can be activated by a variety of stimuli. Previous analysis of chromatin accessibility to DNaseI demonstrated open chromatin conformation of the TNF proximal promoter in T cells. Here, using chromatin probing with restriction enzyme EcoNI and micrococcal nuclease we show that in contrast to the proximal promoter, the TNF transcription start site remains in a closed chromatin configuration in primary T helper (Th) cells, but acquires an open state after activation or polarization under Th1 and Th17 conditions. We further demonstrate that transcription factor c-Jun plays a pivotal role in the maintenance of open chromatin conformation at the transcription start site of the TNF gene.
肿瘤坏死因子(TNF)是免疫系统中关键的初级反应基因之一,可被多种刺激激活。先前对 DNaseI 可及性染色质的分析表明,T 细胞中 TNF 近端启动子具有开放的染色质构象。在这里,我们使用 EcoNI 限制性内切酶和微球菌核酸酶进行染色质探测,结果表明,与近端启动子不同,TNF 转录起始位点在原代辅助性 T 细胞(Th)中仍处于封闭的染色质构型,但在 Th1 和 Th17 条件下激活或极化后会呈现开放状态。我们进一步证明转录因子 c-Jun 在 TNF 基因转录起始位点开放染色质构象的维持中发挥关键作用。