Transcriptional silencers in Drosophila serve a dual role as transcriptional enhancers in alternate cellular contexts. Gisselbrecht et al.

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. Strikingly, almost all transcriptional silencers 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 form 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 human. This dataset contains the raw imaging data (fluorescence photomicrographs of Drosophila embryos) used (after cropping, rotating, and resizing) to produce the figures in this paper. .zvi and .czi files can be opened with ZEN lite software, which is a free download at: https://www.zeiss.com/microscopy/us/products/microscope-software/zen-lite.html

生物学领域的核心挑战之一，在于解析基因组如何编码出复杂的基因表达模式。尽管转录增强子（transcriptional enhancer）已被广泛研究，但迄今已鉴定的转录沉默子（transcriptional silencer）数量极少，且对其功能机制的认知仍十分有限。本研究采用全新筛选策略，在完整果蝇胚胎中对数百条序列开展组织特异性沉默子活性检测。令人瞩目的是，本研究鉴定出的几乎所有转录沉默子，在其他细胞环境中同时具备增强子活性。此类元件结合的转录因子数量显著多于非沉默子序列。其中一部分沉默子可与靶启动子形成远程相互作用。沉默子的缺失会导致其靶基因出现表达去抑制现象。本研究结果对"将增强子与沉默子视为两类独立调控元件"的通用研究范式提出了挑战，并提示在果蝇基因组中尚有数千乃至更多的双功能顺式调控模块（cis-regulatory module, CRM）有待发现，而人类基因组中此类元件的数量可能达到10^4至10^5个。本数据集包含了用于生成本文各图的原始成像数据——果蝇胚胎的荧光显微照片，该数据经裁剪、旋转与尺寸调整后用于论文绘图。.zvi与.czi格式文件可通过ZEN lite软件打开，该软件可免费下载于：https://www.zeiss.com/microscopy/us/products/microscope-software/zen-lite.html