'Insulator bodies' are aggregates of proteins but not of insulators

'Insulator bodies' are aggregates of proteins but not of insulators
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DOI:
10.1038/embor.2008.32
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发表时间:
2008-05-01
期刊:
影响因子:
7.7
通讯作者:
Georgiev, Pavel
Georgiev, Pavel
中科院分区:
生物学2区
文献类型:
--
作者:
Golovnin, Anton;Melnikova, Larisa;Georgiev, Pavel

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染色质绝缘体被认为限制增强剂和沉默剂的作用。果蝇中最著名的绝缘子需要蛋白质如毛翅抑制子(Suppressor of Hairy wing,Su(Hw))和mdg 4修饰子(Modifier of mdg 4,Mod(mdg 4))才能发挥功能。在免疫染色的细胞中,与绝缘子相关的蛋白质明显地以核斑点的形式共定位。有人断言,这些斑点是许多Su(Hw)-绝缘子DNA位点的“绝缘体”,这些绝缘体通过相关蛋白(包括Mod(mdg 4))保持在一起。正如我们在这里使用果蝇、幼虫和S2细胞所显示的,缺乏富Q结构域的突变Mod(mdg 4)蛋白支持Su(Hw)依赖性绝缘子的功能,并有效地结合到染色体上的正确绝缘子位点,但不形成或进入Su(Hw)标记的核斑点;相反,后者积累了另一个(C截短)Mod(mdg 4)突变体,该突变体不能与Su(Hw)或真正的绝缘子相互作用。因此,它不是功能性基因组绝缘体,而是聚集的蛋白质,使所谓的“绝缘体”。
Chromatin insulators are thought to restrict the action of enhancers and silencers. The best-known insulators in Drosophila require proteins such as Suppressor of Hairy wing (Su(Hw)) and Modifier of mdg4 (Mod(mdg4)) to be functional. The insulator-related proteins apparently colocalize as nuclear speckles in immunostained cells. It has been asserted that these speckles are 'insulator bodies' of many Su(Hw)-insulator DNA sites held together by associated proteins, including Mod(mdg4). As we show here using flies, larvae and S2 cells, a mutant Mod(mdg4) protein devoid of the Q-rich domain supports the function of Su(Hw)-dependent insulators and efficiently binds to correct insulator sites on the chromosome, but does not form or enter the Su(Hw)-marked nuclear speckles; conversely, the latter accumulate another (C-truncated) Mod(mdg4) mutant that cannot interact with Su(Hw) or with the genuine insulators. Hence, it is not the functional genomic insulators but rather aggregated proteins that make the so-called 'insulator bodies'.