Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 430 East 67(th) Street, New York, NY 10065, USA.
Cell Rep. 2013 Aug 15;4(3):445-53. doi: 10.1016/j.celrep.2013.07.001. Epub 2013 Aug 1.
A quantitative nucleosome occupancy assay revealed rules for nucleosome disposition in yeast and showed how disposition affects regulation of the GAL genes. Here, we show how those findings apply to the control of Kit, a mammalian gene. The Kit promoter lies in a CpG island, and its enhancer (active in mast cells) lies some 150 kb upstream. Nucleosomes form with especially high avidities at the Kit promoter, a reaction that, we surmise, ensures extremely low basal expression. In mast cells, transcriptional activators displace nucleosomes that are less tightly formed at the Kit enhancer. In turn, the active enhancer replaces a single Kit promoter nucleosome with the transcriptional machinery, thereby inducing transcription over 1,000-fold. As at the yeast GAL genes, the inhibitory effects of nucleosomes facilitate high factors of induction by mammalian activators working in the absence of specific repressors.
一种定量核小体占有率分析方法揭示了核小体在酵母中的排布规律，并展示了这种排布如何影响 GAL 基因的调控。在这里，我们展示了这些发现如何适用于哺乳动物基因 Kit 的调控。Kit 启动子位于 CpG 岛上，其增强子（在肥大细胞中活跃）位于上游约 150kb 处。核小体在 Kit 启动子处形成的亲和力特别高，我们推测，这种反应确保了极低的基础表达。在肥大细胞中，转录激活因子取代了在 Kit 增强子处形成不太紧密的核小体。反过来，活跃的增强子用转录机制取代了一个 Kit 启动子核小体，从而诱导转录超过 1000 倍。与酵母 GAL 基因一样，核小体的抑制作用通过在没有特定抑制剂的情况下发挥作用的哺乳动物激活因子，促进了更高的诱导倍数。
