Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9460-4. doi: 10.1073/pnas.1102625108. Epub 2012 May 29.
Transcriptional repressors are thought to inhibit gene expression by interfering with the binding or function of RNA Polymerase II, perhaps by promoting local chromatin condensation. Here, we present evidence for a distinctive mechanism of repression, whereby sequence-specific repressors prevent the looping of distal enhancers to the promoter. Particular efforts focus on the Snail repressor, which plays a conserved role in promoting epithelial-mesenchyme transitions in both invertebrates and vertebrates, including mesoderm invagination in Drosophila, neural crest migration in vertebrates, and tumorigenesis in mammals. Chromosome conformation capture experiments were used to examine enhancer looping at Snail target genes in wild-type and mutant embryos. These studies suggest that the Snail repressor blocks the formation of fruitful enhancer-promoter interactions when bound to a distal enhancer. This higher-order mechanism of transcriptional repression has broad implications for the control of gene activity in metazoan development.
转录抑制剂被认为通过干扰 RNA 聚合酶 II 的结合或功能来抑制基因表达，可能通过促进局部染色质凝聚。在这里，我们提出了一种独特的抑制机制的证据，即序列特异性抑制剂阻止远端增强子与启动子的环化。特别关注的是 Snaill 抑制剂，它在促进无脊椎动物和脊椎动物中的上皮-间充质转化中发挥保守作用，包括果蝇中的中胚层内陷、脊椎动物中的神经嵴迁移以及哺乳动物中的肿瘤发生。染色体构象捕获实验用于检查野生型和突变型胚胎中 Snaill 靶基因的增强子环化。这些研究表明，当 Snaill 抑制剂结合到远端增强子时，它会阻止有意义的增强子-启动子相互作用的形成。这种转录抑制的高级机制对后生动物发育中基因活性的控制具有广泛的影响。
