Zhang Daoyong, Bai Lu
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802;
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802; Department of Physics, The Pennsylvania State University, University Park, PA 16802
Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4428-33. doi: 10.1073/pnas.1601003113. Epub 2016 Apr 4.
InDrosophila, homologous chromosome pairing leads to "transvection," in which the enhancer of a gene can regulate the allelic transcription intrans.Interallelic interactions were also observed in vegetative diploid budding yeast, but their functional significance is unknown. Here, we show that aGAL1reporter can interact with its homologous allele and affect its expression. By ectopically inserting two allelic reporters, one driven by wild-typeGAL1promoter (WTGAL1pr) and the other by a mutant promoter with delayed response to galactose induction, we found that the two reporters physically associate, and the WTGAL1prtriggers synchronized firing of the defective promoter and accelerates its activation without affecting its steady-state expression level. This interaction and the transregulatory effect disappear when the same reporters are located at nonallelic sites. We further demonstrated that the activator Gal4 is essential for the interallelic interaction, and the transregulation requires fully activated WTGAL1prtranscription. The mechanism of this phenomenon was further discussed. Taken together, our data revealed the existence of interallelic gene regulation in yeast, which serves as a starting point for understanding long-distance gene regulation in this genetically tractable system.
在果蝇中,同源染色体配对会导致“转位效应”,即基因的增强子能够调控等位基因的转录。在营养型二倍体出芽酵母中也观察到了等位基因间的相互作用,但其功能意义尚不清楚。在这里,我们表明一个GAL1报告基因能够与其同源等位基因相互作用并影响其表达。通过异位插入两个等位基因报告基因,一个由野生型GAL1启动子(WTGAL1pr)驱动,另一个由对半乳糖诱导反应延迟的突变启动子驱动,我们发现这两个报告基因在物理上相互关联,并且WTGAL1pr触发了有缺陷启动子的同步激发并加速其激活,而不影响其稳态表达水平。当相同的报告基因位于非等位位点时,这种相互作用和反式调控效应消失。我们进一步证明激活因子Gal4对于等位基因间的相互作用至关重要,并且反式调控需要完全激活的WTGAL1pr转录。我们对这一现象的机制进行了进一步讨论。综上所述,我们的数据揭示了酵母中等位基因间基因调控的存在,这为理解这个遗传易处理系统中的长距离基因调控提供了一个起点。