Developmental enhancers and chromosome topology.

Developmental enhancers and chromosome topology.
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DOI:
10.1126/science.aau0320
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发表时间:
2018-09-28
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Levine M
Levine M
中科院分区:
其他
文献类型:
--
作者:
Furlong EEM;Levine M

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在后生动物胚胎发生的特定阶段,发育增强子介导特定细胞类型的基因表达的开/关模式。它们通常整合多个信号和调控决定因素,以实现精确的时空表达。这些增强子可以从它们所调节的基因中绘制出一个甚至更多的碱基。远程增强子如何将调控信息传递给它们的目标启动子是基因组组织和功能的核心奥秘之一。多年来,人们提出了各种不同的机制,包括增强子跟踪、连接、循环和向转录工厂的动员。我们认为这些机制的极端版本不能解释在活细胞、组织和胚胎中看到的转录动力学和精度。我们描述了动态三维枢纽的新证据,它结合了经典模型的不同元素。
Developmental enhancers mediate on/off patterns of gene expression in specific cell types at particular stages during metazoan embryogenesis. They typically integrate multiple signals and regulatory determinants to achieve precise spatiotemporal expression. Such enhancers can map quite far—one megabase or more—from the genes they regulate. How remote enhancers relay regulatory information to their target promoters is one of the central mysteries of genome organization and function. A variety of contrasting mechanisms have been proposed over the years, including enhancer tracking, linking, looping, and mobilization to transcription factories. We argue that extreme versions of these mechanisms cannot account for the transcriptional dynamics and precision seen in living cells, tissues, and embryos. We describe emerging evidence for dynamic three-dimensional hubs that combine different elements of the classical models.
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