Transcriptional Silencers in Drosophila Serve a Dual Role as Transcriptional Enhancers in Alternate Cellular Contexts
Transcriptional Silencers in Drosophila Serve a Dual Role as Transcriptional Enhancers in Alternate Cellular Contexts
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DOI：
10.1016/j.molcel.2019.10.004
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发表时间：
2020-01-16
期刊：
影响因子：
16
通讯作者：
Bulyk, Martha L.
中科院分区：
文献类型：
--
作者：
Gisselbrecht, Stephen S.;Palagi, Alexandre;Bulyk, Martha L.
生物学的一个主要挑战是了解复杂的基因表达模式是如何在基因组中编码的。虽然转录增强子已被广泛研究，但很少有转录沉默子被鉴定出来，而且对它们的了解仍然很少。在这里，我们使用了一种新的策略来筛选整个果蝇胚胎中组织特异性沉默子活性的数百个序列。我们发现的几乎所有转录沉默子在其他细胞环境中也是活跃的增强子。这些元件比非沉默子被更多的转录因子结合。这些沉默者的一个子集与启动子形成长距离接触。沉默子的缺失导致其靶基因的去阻遏。我们的研究结果挑战了将增强子和沉默子作为不同类别的调节元件处理的常见做法，并表明在果蝇和人类中仍有可能发现数千个或更多的双功能CRM。
A major challenge in biology is to understand how complex gene expression patterns are encoded in the genome. While transcriptional enhancers have been studied extensively, few transcriptional silencers have been identified, and they remain poorly understood. Here, we used a novel strategy to screen hundreds of sequences for tissue-specific silencer activity in whole Drosophila embryos. Almost all of the transcriptional silencers that we identified were also active enhancers in other cellular contexts. These elements are bound by more transcription factors than non-silencers. A subset of these silencers forms long-range contacts with promoters. Deletion of a silencer caused derepression of its target gene. Our results challenge the common practice of treating enhancers and silencers as separate classes of regulatory elements and suggest the possibility that thousands or more bifunctional CRMs remain to be discovered in Drosophila and 10(4)-10(5) in humans.