A Direct Role for Cohesin in Gene Regulation and Ecdysone Response in Drosophila Salivary Glands
A Direct Role for Cohesin in Gene Regulation and Ecdysone Response in Drosophila Salivary Glands
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DOI：
10.1016/j.cub.2010.09.006
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发表时间：
2010-10-26
期刊：
影响因子：
9.2
通讯作者：
Nasmyth, Kim
中科院分区：
文献类型：
--
作者：
Pauli, Andrea;van Bemmel, Joke G.;Nasmyth, Kim
背景：Cornelia de Lange 综合征中观察到的发育异常与粘连蛋白机制的突变存在遗传相关性。这些和其他最近的实验结果表明，粘连蛋白除了其介导姐妹染色单体凝聚力的典型功能外，还可能参与调节基因表达。 结果：我们报告，有丝分裂后果蝇唾液腺中粘连蛋白的 kleisin 亚基的裂解诱导许多基因转录水平的重大变化。对粘连蛋白裂解时转录水平变化的动力学分析表明，一部分基因在几个小时内对粘连蛋白裂解做出反应。此外，粘连蛋白与大多数这些位点结合，表明粘连蛋白直接调节它们的表达。这些基因中有几个是受类固醇激素蜕皮激素调节的。对选定的蜕皮激素反应基因的转录进行细胞学可视化显示，Eip74EF 的膨胀会在粘连蛋白裂解后的一两个小时内停止，远远早于在此位点检测到蜕皮激素受体的任何下降。 结论：我们得出结论，粘连蛋白调节一组不同基因的表达，包括那些介导蜕皮激素反应的基因。
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.