The interaction landscape between transcription factors and the nucleosome.

The interaction landscape between transcription factors and the nucleosome.
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DOI:
10.1038/s41586-018-0549-5
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发表时间:
2018-10
期刊:
影响因子:
64.8
通讯作者:
Taipale J
Taipale J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhu F;Farnung L;Kaasinen E;Sahu B;Yin Y;Wei B;Dodonova SO;Nitta KR;Morgunova E;Taipale M;Cramer P;Taipale J

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核小体覆盖基因组的大部分,并且被认为在指导基因表达的区域中被转录因子(TF)置换。然而,转录因子和核小体DNA之间的相互作用模式在很大程度上仍然未知。在这里,我们系统地探讨了核小体和代表不同结构家族的220个TF之间的相互作用。与早期的观察相一致,我们发现大多数研究的TF比游离DNA更少接触核小体DNA。从与核小体和游离DNA结合的TF中回收的基序通常是相似的;然而,核小体的空间位阻和支架导致基序的特定定位和取向。许多TF优先结合到核小体DNA的末端附近,或其溶剂暴露侧的周期性位置。TF通常也以特定的方向与核小体DNA结合。一些TF特异性地与位于二分体位置的DNA相互作用,其中只有一个DNA回旋被缠绕,而其他TF更喜欢跨越两个DNA回旋的位点,并特异性地与它们中的每一个结合。我们的工作揭示了TF与游离DNA和核小体DNA结合的显著差异,并揭示了TF与核小体之间丰富的相互作用景观。
Nucleosomes cover most of the genome and are thought to be displaced by transcription factors (TFs) in regions that direct gene expression. However, the modes of interaction between TFs and nucleosomal DNA remain largely unknown. Here, we have systematically explored interactions between the nucleosome and 220 TFs representing diverse structural families. Consistently with earlier observations, we find that the majority of the studied TFs have less access to nucleosomal DNA than to free DNA. The motifs recovered from TFs 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 TFs preferentially bind close to the end of nucleosomal DNA, or to periodic positions at its solvent-exposed side. TFs often also bind to nucleosomal DNA in a particular orientation. Some TFs specifically interact with DNA located at the dyad position where only one DNA gyre is wound, whereas other TFs prefer sites spanning two DNA gyres and bind specifically to each of them. Our work reveals striking differences in TF binding to free and nucleosomal DNA, and uncovers a rich interaction landscape between TFs and the nucleosome.
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