Melnikova Larisa, Biryukova Inna, Kan Tatyana, Georgiev Pavel
Department of the Control of Genetic Processes, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov st, Moscow, 119334, Russia.
Chromosoma. 2008 Feb;117(1):41-50. doi: 10.1007/s00412-007-0124-6. Epub 2007 Sep 18.
In Drosophila melanogaster, broken chromosome ends behave as real telomeres and are believed to be covered with telomere-specific chromatin. It has been shown previously that the telomeric chromatin represses normal activity of enhancers that regulate yellow expression in wings and body cuticle. In this paper, we have found that a modified yellow promoter is fully active in the wing and body cuticle when it is located at the chromosome end, which is evidence that the telomeric chromatin does not repress transcription. Substitution of the yellow core promoter region, including TATA and Inr, with the promoter regions of the eve, hsp70 (TATA-containing), and white (TATA-less) promoters does not affect the ability of the promoter to be cis- or trans-activated by the yellow enhancers if the heterologous promoter is located at a distance of about 6 kb from the chromosome end. The best characterized Drosophila insulator found in the gypsy retrotransposon can specifically repress the yellow promoter at a distance when one component of the insulator complex, Mod(mdg4)-67.2 protein, is inactive. We have also found that, in the mod(mdg4) mutant background, the gypsy insulator can repress the heterologous promoters, indicating that the core promoter elements are not critical for specificity of repression. However, long-distance functional enhancer-promoter and gypsy-promoter interactions were suppressed when the distance between the yellow promoter and the end of the deficient chromosome was less than 6 kb. These results suggest that Drosophila telomeric chromatin does not generally repress transcription but is somehow involved in suppression of some long-distance interactions between regulatory elements.
在黑腹果蝇中,断裂的染色体末端表现得如同真正的端粒,并且被认为覆盖着端粒特异性染色质。先前已经表明,端粒染色质会抑制调控翅膀和体表角质层中黄色素表达的增强子的正常活性。在本文中,我们发现当一个经过修饰的黄色素启动子位于染色体末端时,它在翅膀和体表角质层中具有完全活性,这证明端粒染色质并不抑制转录。如果异源启动子位于距离染色体末端约6 kb处,用eve、hsp70(含TATA)和白色(不含TATA)启动子的启动子区域替换黄色素核心启动子区域(包括TATA和Inr),不会影响该启动子被黄色素增强子顺式或反式激活的能力。在gypsy逆转座子中发现的最具特征的果蝇绝缘子,当绝缘子复合体的一个组分Mod(mdg4)-67.2蛋白无活性时,能够在一定距离外特异性抑制黄色素启动子。我们还发现,在mod(mdg4)突变背景下,gypsy绝缘子能够抑制异源启动子,这表明核心启动子元件对于抑制特异性并非至关重要。然而,当黄色素启动子与缺失染色体末端之间的距离小于6 kb时,长距离功能性增强子 - 启动子和gypsy - 启动子相互作用受到抑制。这些结果表明,果蝇端粒染色质一般不抑制转录,但以某种方式参与抑制调控元件之间的一些长距离相互作用。