Dynamic Reconfiguration of Long Human Genes during One Transcription Cycle
Dynamic Reconfiguration of Long Human Genes during One Transcription Cycle
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DOI：
10.1128/mcb.00179-12
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发表时间：
2012-07-01
影响因子：
5.3
通讯作者：
Papantonis, Argyris
中科院分区：
文献类型：
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作者：
Larkin, Joshua D.;Cook, Peter R.;Papantonis, Argyris
我们分析了三个长度>200 kbp的人类基因，因为它们被肿瘤坏死因子α快速同步地打开，并获得了对转录周期的新见解，这是使用连续活性的短基因难以获得的。首先，一个基因中预先存在的“全基因”环在刺激时消失;它被CCCTC结合因子和TFIIB稳定，并使基因保持快速反应。其次，“亚基因”环（使用染色体构象捕获检测）发展和扩大，如果延伸聚合酶在转录工厂中固定下来，在那里它们卷起模板，那么这个结果就可以简单地解释。第三，高分辨率定位证实，相关的新生转录本（使用RNA荧光原位杂交检测）位于足够接近的一个工厂的表面上。这些动态强调了平衡，启动和延长转录状态之间的复杂转换。
We analyzed three human genes that were >200 kbp in length as they are switched on rapidly and synchronously by tumor necrosis factor alpha and obtained new insights into the transcription cycle that are difficult to obtain using continuously active, short, genes. First, a preexisting "whole-gene" loop in one gene disappears on stimulation; it is stabilized by CCCTC-binding factor and TFIIB and poises the gene for a prompt response. Second, "subgene" loops (detected using chromosome conformation capture) develop and enlarge, a result that is simply explained if elongating polymerases become immobilized in transcription factories, where they reel in their templates. Third, high-resolution localization confirms that relevant nascent transcripts (detected using RNA fluorescence in situ hybridization) lie close enough to be present on the surface of one factory. These dynamics underscore the complex transitions between the poised, initiating, and elongating transcriptional states.