Morcillo P, Rosen C, Dorsett D
Molecular Biology Program, Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Genetics. 1996 Nov;144(3):1143-54. doi: 10.1093/genetics/144.3.1143.
The mechanisms that allow enhancers to activate promoters from thousands of base pairs away are disrupted by the suppressor of Hairy-wing protein (SUHW) of Drosophila. SUHW binds a DNA sequence in the gypsy retrotransposon and prevents enhancers promoter-distal to a gypsy insertion in a gene from activating without affecting promoter-proximal enhancers. Several observations indicate that SUHW does not affect enhancer-binding activators. Instead, SUHW may interfere with factors that structurally facilitate interactions between an enhancer and promoter. To identify putative enhancer facilitators, a screen for mutations that reduce activity of the remote wing margin enhancer in the cut gene was performed. Mutations in scalloped, mastermind, and a previously unknown gene, Chip, were isolated. A TEA DNA-binding domain in the Scalloped protein binds the wing margin enhancer. Interactions between scalloped, mastermind and Chip mutations indicate that mastermind and Chip act synergistically with scalloped to regulate the wing margin enhancer. Chip is essential and also affects expression of a gypsy insertion in Ultrabithorax. Relative to mutations in scalloped or mastermind, a Chip mutation hypersensitizes the wing margin enhancer in cut to gypsy insertions. Therefore, Chip might encode a target of SUHW enhancer-blocking activity.
果蝇的毛翅蛋白抑制因子(SUHW)破坏了增强子从数千个碱基对之外激活启动子的机制。SUHW与逆转座子gypsy中的一个DNA序列结合,并阻止基因中gypsy插入位点远端的增强子激活启动子,而不影响启动子近端的增强子。多项观察结果表明,SUHW不影响与增强子结合的激活因子。相反,SUHW可能会干扰在结构上促进增强子与启动子之间相互作用的因子。为了鉴定假定的增强子促进因子,对降低cut基因中远端翅缘增强子活性的突变进行了筛选。分离出了在扇形基因(scalloped)、主谋基因(mastermind)和一个以前未知的基因Chip中的突变。扇形蛋白中的一个TEA DNA结合结构域与翅缘增强子结合。扇形、主谋和Chip突变之间的相互作用表明,主谋和Chip与扇形协同作用来调节翅缘增强子。Chip是必需的,并且还影响双胸基因(Ultrabithorax)中gypsy插入的表达。相对于扇形或主谋中的突变,Chip突变使cut基因中的翅缘增强子对gypsy插入更加敏感。因此,Chip可能编码SUHW增强子阻断活性的一个靶点。