Barolo S, Levine M
Department of Biology, Center for Molecular Genetics, University of California at San Diego, La Jolla 92093-0366, USA.
EMBO J. 1997 May 15;16(10):2883-91. doi: 10.1093/emboj/16.10.2883.
hairy encodes a bHLH repressor that regulates several developmental processes in Drosophila, including embryonic segmentation and neurogenesis. Segmentation repressors such as Krüppel and knirps have been shown to function over short distances, less than 50-100 bp, to inhibit or quench closely linked upstream activators. This mode of repression permits multiple enhancers to work independently of one another within a modular promoter. Here, we employ a transgenic embryo assay to present evidence that hairy acts as a dominant repressor, which can function over long distances to block multiple enhancers. hairy is shown to repress a heterologous enhancer, the rhomboid NEE, when bound 1 kb from the nearest upstream activator. Moreover, the binding of hairy to a modified NEE leads to the repression of both the NEE and a distantly linked mesoderm-specific enhancer within a synthetic modular promoter. Additional evidence that hairy is distinct from previously characterized embryonic repressors stems from the analysis of the gypsy insulator DNA. This insulator selectively blocks the hairy repressor, but not the linked activators, within a modified NEE. We compare hairy with previously characterized repressors and discuss the consequences of short-range and long-range repression in development.
“hairy”编码一种bHLH阻遏物，它调控果蝇中的多个发育过程，包括胚胎体节形成和神经发生。诸如Krüppel和knirps等体节形成阻遏物已被证明在小于50 - 100碱基对的短距离内发挥作用，以抑制或淬灭紧密相连的上游激活因子。这种阻遏模式允许多个增强子在模块化启动子内彼此独立发挥作用。在这里，我们采用转基因胚胎检测来提供证据，证明“hairy”作为一种显性阻遏物，可以在长距离发挥作用以阻断多个增强子。当“hairy”与最接近的上游激活因子相距1千碱基结合时，它能抑制一个异源增强子——rhomboid NEE。此外，“hairy”与修饰后的NEE结合会导致在合成模块化启动子内NEE和一个远距离相连的中胚层特异性增强子均被抑制。“hairy”与先前表征的胚胎阻遏物不同的其他证据来自对gypsy绝缘子DNA的分析。在修饰后的NEE中，这种绝缘子选择性地阻断“hairy”阻遏物，但不阻断相连的激活因子。我们将“hairy”与先前表征的阻遏物进行比较，并讨论发育过程中短程和长程阻遏的后果。
