黏合蛋白在果蝇唾液腺基因调控和蜕皮激素反应中的直接作用。
A direct role for cohesin in gene regulation and ecdysone response in Drosophila salivary glands.
机构信息
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK.
出版信息
Curr Biol. 2010 Oct 26;20(20):1787-98. doi: 10.1016/j.cub.2010.09.006. Epub 2010 Oct 7.
BACKGROUND
Developmental abnormalities observed in Cornelia de Lange syndrome have been genetically linked to mutations in the cohesin machinery. These and other recent experimental findings have led to the suggestion that cohesin, in addition to its canonical function of mediating sister chromatid cohesion, might also be involved in regulating gene expression.
RESULTS
We report that cleavage of cohesin's kleisin subunit in postmitotic Drosophila salivary glands induces major changes in the transcript levels of many genes. Kinetic analyses of changes in transcript levels upon cohesin cleavage reveal that a subset of genes responds to cohesin cleavage within a few hours. In addition, cohesin binds to most of these loci, suggesting that cohesin is directly regulating their expression. Among these genes are several that are regulated by the steroid hormone ecdysone. Cytological visualization of transcription at selected ecdysone-responsive genes reveals that puffing at Eip74EF ceases within an hour or two of cohesin cleavage, long before any decline in ecdysone receptor could be detected at this locus.
CONCLUSION
We conclude that cohesin regulates expression of a distinct set of genes, including those mediating the ecdysone response.
背景
Cornelia de Lange 综合征中观察到的发育异常与黏合蛋白机制的突变有关。这些以及其他最近的实验发现表明，黏合蛋白除了介导姐妹染色单体黏合的典型功能外，还可能参与调节基因表达。
结果
我们报告称，在后有丝分裂的果蝇唾液腺中，黏合蛋白 kleisin 亚基的切割诱导了许多基因的转录水平发生重大变化。对黏合蛋白切割后转录水平变化的动力学分析表明，有一部分基因在几小时内对黏合蛋白切割作出反应。此外，黏合蛋白与大多数这些基因座结合，表明黏合蛋白直接调控它们的表达。其中包括一些受类固醇激素蜕皮激素调节的基因。在选定的蜕皮激素反应基因中对转录进行细胞学可视化显示，在黏合蛋白切割后一两个小时内，Eip74EF 泡的膨突就停止了，而在这个基因座上检测到蜕皮激素受体的任何下降之前。
结论
我们得出结论，黏合蛋白调节一组独特基因的表达，包括那些介导蜕皮激素反应的基因。
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