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The interaction landscape between transcription factors and the nucleosome

机译:转录因子与核小体之间的相互作用

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摘要

Nucleosomes cover most of the genome and are thought to be displaced by transcription factors in regions that direct gene expression. However, the modes of interaction between transcription factors and nucleosomal DNA remain largely unknown. Here we systematically explore interactions between the nucleosome and 220 transcription factors representing diverse structural families. Consistent with earlier observations, we find that the majority of the studied transcription factors have less access to nucleosomal DNA than to free DNA. The motifs recovered from transcription factors bound to nucleosomal and free DNA are generally similar. However, steric hindrance and scaffolding by the nucleosome result in specific positioning and orientation of the motifs. Many transcription factors preferentially bind close to the end of nucleosomal DNA, or to periodic positions on the solvent-exposed side of the DNA. In addition, several transcription factors usually bind to nucleosomal DNA in a particular orientation. Some transcription factors specifically interact with DNA located at the dyad position at which only one DNA gyre is wound, whereas other transcription factors prefer sites spanning two DNA gyres and bind specifically to each of them. Our work reveals notable differences in the binding of transcription factors to free and nucleosomal DNA, and uncovers a diverse interaction landscape between transcription factors and the nucleosome.
机译:核小体覆盖了大部分基因组,并被认为在指导基因表达的区域中被转录因子置换。但是,转录因子和核小体DNA之间的相互作用模式仍然是未知的。在这里,我们系统地探索核小体和代表不同结构家族的220个转录因子之间的相互作用。与早期的观察结果一致,我们发现大多数研究的转录因子与游离DNA相比,对核小体DNA的访问较少。从结合到核小体和游离DNA的转录因子回收的基序通常是相似的。但是,核小体的空间位阻和支架导致了基序的特定定位和方向。许多转录因子优先结合在核小体DNA的末端附近或DNA溶剂暴露侧的周期性位置。另外,几种转录因子通常以特定的方向与核小体DNA结合。一些转录因子与位于仅缠绕一个DNA回旋体的二分体位置的DNA发生特异性相互作用,而其他转录因子更喜欢跨越两个DNA回旋体的位点并特异性地与每个DNA回旋体结合。我们的工作揭示了转录因子与游离DNA和核小体DNA结合的显着差异,并揭示了转录因子与核小体之间的多种相互作用。

著录项

  • 来源
    《Nature》 |2018年第7725期|76-81|共6页
  • 作者单位

    Univ Cambridge, Dept Biochem, Cambridge, England;

    Max Planck Inst Biophys Chem, Dept Mol Biol, Gottingen, Germany;

    Karolinska Inst, Dept Med Biochem & Biophys, Div Funct Genom & Syst Biol, Stockholm, Sweden;

    Univ Helsinki, Genome Scale Biol Program, Helsinki, Finland;

    Karolinska Inst, Dept Med Biochem & Biophys, Div Funct Genom & Syst Biol, Stockholm, Sweden;

    Karolinska Inst, Dept Med Biochem & Biophys, Div Funct Genom & Syst Biol, Stockholm, Sweden;

    Max Planck Inst Biophys Chem, Dept Mol Biol, Gottingen, Germany;

    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden;

    Karolinska Inst, Dept Med Biochem & Biophys, Div Funct Genom & Syst Biol, Stockholm, Sweden;

    Univ Cambridge, Dept Biochem, Cambridge, England;

    Max Planck Inst Biophys Chem, Dept Mol Biol, Gottingen, Germany;

    Univ Cambridge, Dept Biochem, Cambridge, England;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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