Scott K S, Geyer P K
Department of Biochemistry, University of Iowa, College of Medicine, Iowa City 52242, USA.
EMBO J. 1995 Dec 15;14(24):6258-67. doi: 10.1002/j.1460-2075.1995.tb00316.x.
The suppressor of Hairy-wing [su(Hw)] protein mediates the mutagenic effects of the gypsy retrotransposon by blocking enhancer activity. These repressive effects are general, can occur over long distances and require that the su(Hw) protein is bound between the affected enhancer and promoter. The effects of the su(Hw) binding region on yolk protein (yp) gene expression were determined. These genes are regulated by shared enhancers in the intergenic region, which provided a method to examine whether an enhancer blocked by the su(Hw) protein remained functional. We demonstrate that a blocked enhancer is completely active, supporting the proposal that the su(Hw) protein is an insulator protein that acts by forming a new boundary in a pre-existing chromatin domain, thereby preventing the interaction of regulatory elements located upstream of the insertion site with the promoter. In addition, we found that yp promoter function is not diminished by sharing enhancers, suggesting that these enhancers are not rate limiting for transcriptional activation. Lastly, our data indicate that yp promoter activity is interdependent, such that transcription from one promoter influences the level of activity of the linked promoter.
毛翅抑制因子[su(Hw)]蛋白通过阻断增强子活性介导了吉普赛逆转座子的诱变效应。这些抑制作用具有普遍性,可在长距离上发生,并且要求su(Hw)蛋白结合在受影响的增强子和启动子之间。确定了su(Hw)结合区域对卵黄蛋白(yp)基因表达的影响。这些基因由基因间区域中的共享增强子调控,这提供了一种方法来检验被su(Hw)蛋白阻断的增强子是否仍具有功能。我们证明,被阻断的增强子完全具有活性,这支持了su(Hw)蛋白是一种绝缘子蛋白的观点,它通过在预先存在的染色质结构域中形成新的边界来发挥作用,从而阻止插入位点上游的调控元件与启动子相互作用。此外,我们发现共享增强子不会降低yp启动子的功能,这表明这些增强子对转录激活不是限速因素。最后,我们的数据表明yp启动子活性是相互依赖的,以至于来自一个启动子的转录会影响相连启动子的活性水平。