NF-κB is a transcription factor responsible for activating hundreds of genes in mammalian organisms. To accomplish its function, NF-κB must interact with DNA occupied by nucleosomes, but how this interaction occurs is unclear. Here we used Atomic Force Microscopy to characterize complexes of NF-κB with nucleosomes assembled on different DNA templates. The assembly of NF-κB-nucleosome complexes leads to a substantial decrease of DNA wrapping efficiency from 149 ± 2 bp (SEM) for the control nucleosome sample to 135 ± 3 bp for complexes of nucleosomes with NF-κB. Mapping of the nucleosomes did not reveal displacement of under-wrapped nucleosomes from their original position, suggesting that unravelling involves dissociation of one or both flanks of the nucleosomes. Binding of NF-κB to the core was identified by nucleosome core volume measurements. We discovered two binding modes of NF-κB associated with nucleosome unravelling - NF-κB bound to the nucleosome core and to the DNA flanks. From these findings we propose two models explaining the interaction of NF-κB with the nucleosome complex. The partial unravelling of nucleosomes by NF-κB makes the DNA segment at the edge of the nucleosome core accessible, facilitating the transcription process. We speculate that NF-κB can function as a pioneer factor, enhancing its ability to facilitate rapid transcriptional response to cell stress.

NF-κB 是一种转录因子，负责激活哺乳动物生物体中的数百个基因。为了完成其功能，NF-κB 必须与核小体占据的 DNA 相互作用，但这种相互作用是如何发生的尚不清楚。在这里，我们使用原子力显微镜来表征 NF-κB 与组装在不同 DNA 模板上的核小体的复合物。NF-κB-核小体复合物的组装导致 DNA 包裹效率从对照核小体样品的 149 ± 2 bp (SEM) 大幅降低至核小体与 NF-κB 复合物的 135 ± 3 bp。核小体的映射没有揭示包裹下的核小体从其原始位置的位移，这表明解开涉及核小体的一侧或两侧的解离。通过核小体核心体积测量确定 NF-κB 与核心的结合。我们发现了两种与核小体解体相关的 NF-κB 结合模式——NF-κB 与核小体核心和 DNA 侧翼结合。根据这些发现，我们提出了两个模型来解释 NF-κB 与核小体复合物的相互作用。NF-κB 对核小体的部分解开使核小体核心边缘的 DNA 片段可接近，从而促进转录过程。我们推测 NF-κB 可以作为先驱因子发挥作用，增强其促进对细胞应激的快速转录反应的能力。NF-κB 对核小体的部分解开使核小体核心边缘的 DNA 片段可接近，从而促进转录过程。我们推测 NF-κB 可以作为先驱因子发挥作用，增强其促进对细胞应激的快速转录反应的能力。NF-κB 对核小体的部分解开使核小体核心边缘的 DNA 片段可接近，从而促进转录过程。我们推测 NF-κB 可以作为先驱因子发挥作用，增强其促进对细胞应激的快速转录反应的能力。