A Barrier-Only Boundary Element Delimits the Formation of Facultative Heterochromatin in Drosophila melanogaster and Vertebrates

A Barrier-Only Boundary Element Delimits the Formation of Facultative Heterochromatin in Drosophila melanogaster and Vertebrates
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DOI:
10.1128/mcb.05165-11
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发表时间:
2011-07-01
影响因子:
5.3
通讯作者:
Zhou, Lei
Zhou, Lei
中科院分区:
生物学2区
文献类型:
--
作者:
Lin, Nianwei;Li, Xingguo;Zhou, Lei

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在特定的基因组位点形成兼性异染色质在定义细胞特性如分化潜能和对发育、生理和环境刺激的反应性方面是至关重要的。由于其形成的性质,异染色质和抑制性组蛋白标记会不断繁殖,直到连锁反应被打破。虽然某些活性启动子可以阻断异染色质的增殖,但也有专门的DNA元件,称为染色质屏障,用于划分兼性异染色质形成的边界。在这项研究中,我们确定了一个染色质屏障,专门限制形成的抑制性染色质的远端增强子区域,使抑制性组蛋白修饰不能达到启动子和启动子近端增强子区域的收割机。不同于所有已知的边界元件确定的果蝇,这个IRER(辐射响应增强子区域)左屏障(ILB)不表现出增强子阻断活性。ILB不仅在不同的果蝇物种中是保守的,它还可以在脊椎动物细胞中作为有效的染色质屏障发挥作用。这表明,它的功能,以空间上限制由三甲基化H3K27标记的抑制性染色质的形成的机制也已在进化过程中广泛保守。
Formation of facultative heterochromatin at specific genomic loci is fundamentally important in defining cellular properties such as differentiation potential and responsiveness to developmental, physiological, and environmental stimuli. By the nature of their formation, heterochromatin and repressive histone marks propagate until the chain reaction is broken. While certain active promoters can block propagation of heterochromatin, there are also specialized DNA elements, referred to as chromatin barriers, that serve to demarcate the boundary of facultative heterochromatin formation. In this study, we identified a chromatin barrier that specifically limits the formation of repressive chromatin to a distal enhancer region so that repressive histone modifications cannot reach the promoter and promoter-proximal enhancer regions of reaper. Unlike all of the known boundary elements identified for Drosophila melanogaster, this IRER (irradiation-responsive enhancer region) left barrier (ILB) does not exhibit enhancer-blocking activity. Not only has the ILB been conserved in different Drosophila species, it can also function as an effective chromatin barrier in vertebrate cells. This suggests that the mechanism by which it functions to spatially restrict the formation of repressive chromatin marked by trimethylated H3K27 has also been conserved widely during evolution.