Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Mol Cell. 2018 Apr 19;70(2):287-296.e6. doi: 10.1016/j.molcel.2018.02.029. Epub 2018 Mar 29.
How remote enhancers interact with appropriate target genes persists as a central mystery in gene regulation. Here, we exploit the properties of transvection to explore enhancer-promoter communication between homologous chromosomes in living Drosophila embryos. We successfully visualized the activation of an MS2-tagged reporter gene by a defined developmental enhancer located in trans on the other homolog. This trans-homolog activation depends on insulator DNAs, which increase the stability-but not the frequency-of homolog pairing. A pair of heterotypic insulators failed to mediate transvection, raising the possibility that insulator specificity underlies the formation of chromosomal loop domains. Moreover, we found that a shared enhancer co-activates separate PP7 and MS2 reporter genes incis and intrans. Transvecting alleles weakly compete with one another, raising the possibility that they share a common pool of the transcription machinery. We propose that transvecting alleles form a trans-homolog "hub," which serves as a scaffold for the accumulation of transcription complexes.
远程增强子如何与适当的靶基因相互作用，这在基因调控中仍是一个核心难题。在这里，我们利用转导现象的特性，在活体果蝇胚胎中探索同源染色体之间的增强子-启动子通讯。我们成功地可视化了位于另一条同源染色体上的定义性发育增强子对 MS2 标记报告基因的激活。这种跨同源激活依赖于绝缘子 DNA，它增加了同源配对的稳定性，但不增加同源配对的频率。一对异型绝缘子不能介导转导，这增加了绝缘子特异性是形成染色体环域的可能性。此外，我们发现一个共享的增强子共同激活了分离的 PP7 和 MS2 报告基因 incis 和 intrans。转导等位基因之间存在微弱的竞争，这增加了它们共享一个共同的转录机制池的可能性。我们提出，转导等位基因形成一个跨同源“枢纽”，作为转录复合物积累的支架。
