Effects of DNA supercoiling on chromatin architecture.
Effects of DNA supercoiling on chromatin architecture.
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DNA超螺旋对染色质结构的影响。
DOI：
10.1007/s12551-016-0242-6
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发表时间：
2016
影响因子：
--
通讯作者：
Gilbert, Nick
中科院分区：
文献类型：
--
作者：
Corless, Samuel;Gilbert, Nick
染色质结构的破坏对于真核生物基因组的调控是必要的，从碱基对水平的核小体重塑到数百个碱基大小的大规模染色质结构域。RNA聚合酶是一个强大的马达，由于DNA的螺旋间距太紧，它无法转动，因此在其前面产生过度缠绕的DNA，而在其后面产生欠缠绕的DNA。越来越多的证据支持转录依赖的DNA超螺旋在所有尺度上破坏染色质结构的核心作用。这种超螺旋改变了DNA螺旋的性质，其方式实质上改变了DNA结合蛋白和复合物（包括核小体、聚合酶、拓扑异构酶和转录因子）的结合特异性。例如，瞬时过度缠绕的DNA在转录聚合酶之前使核小体核心颗粒不稳定，而缠绕下的DNA促进转录聚合酶后面的预起始复合物形成、转录因子结合和核小体核心颗粒缔合。重要的是，DNA超螺旋也可以通过DNA消散，即使在染色质化的背景下，影响局部元件和大的染色质结构域。我们提出了一个模型，其中不受约束的DNA超螺旋的变化影响更高水平的染色质组织通过DNA超螺旋的DNA-蛋白质和DNA-核小体相互作用的加性效应。该模型将DNA和染色质的小规模变化与高阶纤维和大规模染色质结构联系起来，提供了一种将基因调控与体内染色质结构相关的机制。
Disruptions in chromatin structure are necessary for the regulation of eukaryotic genomes, from remodelling of nucleosomes at the base pair level through to large-scale chromatin domains that are hundreds of kilobases in size. RNA polymerase is a powerful motor which, prevented from turning with the tight helical pitch of the DNA, generates over-wound DNA ahead of itself and under-wound DNA behind. Mounting evidence supports a central role for transcription-dependent DNA supercoiling in disrupting chromatin structure at all scales. This supercoiling changes the properties of the DNA helix in a manner that substantially alters the binding specificity of DNA binding proteins and complexes, including nucleosomes, polymerases, topoisomerases and transcription factors. For example, transient over-wound DNA destabilises nucleosome core particles ahead of a transcribing polymerase, whereas under-wound DNA facilitates pre-initiation complex formation, transcription factor binding and nucleosome core particle association behind the transcribing polymerase. Importantly, DNA supercoiling can also dissipate through DNA, even in a chromatinised context, to influence both local elements and large chromatin domains. We propose a model in which changes in unconstrained DNA supercoiling influences higher levels of chromatin organisation through the additive effects of DNA supercoiling on both DNA-protein and DNA-nucleosome interactions. This model links small-scale changes in DNA and chromatin to the higher-order fibre and large-scale chromatin structures, providing a mechanism relating gene regulation to chromatin architecture in vivo.