Effects of DNA supercoiling on chromatin architecture

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• 作者：Samuel Corless ; Nick Gilbert
• 关键词：DNA supercoiling ; Protein–DNA ; Gene regulation ; Eukaryotic chromatin ; Genome architecture
• 刊名：Biophysical Reviews
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：8
• 期：3
• 页码：245-258
• 全文大小：1,364 KB
• 刊物类别：Physics and Astronomy
• 刊物主题：Physics
  Biophysics and Biomedical Physics
  Cell Biology
  Biochemistry
  Biological Techniques
  Biomedicine
  Nanotechnology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1867-2469
• 卷排序：8

文摘

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.