Dynamics of nucleosome invasion by DNA binding proteins.
Dynamics of nucleosome invasion by DNA binding proteins.
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DNA 结合蛋白入侵核小体的动力学。
DOI：
10.1016/j.jmb.2011.05.044
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发表时间：
2011
影响因子：
5.6
通讯作者：
Widom,Jonathan
中科院分区：
文献类型：
--
作者：
Tims,HannahS;Gurunathan,Kaushik;Levitus,Marcia;Widom,Jonathan
核小体在空间上封闭它们包裹的DNA，使其不能与许多大的蛋白质复合物相互作用。蛋白质如何在体内进入核小体DNA靶位点尚不清楚。核小体DNA的外部延伸以高频率自发地解开和重新缠绕，提供快速和有效地进入位于那里的调节DNA靶位点;然而，尚未测量进入核小体内部的速率。在这里，我们表明，对于一个选定的高亲和力的核小体定位序列，自发的DNA解包裹率显着降低核小体内的距离。重新包装的速度也会降低，但只是轻微的。我们的研究结果解释了先前已知的强位置依赖于核小体DNA的平衡可及性，这是选择和自然序列的特点。我们的研究结果指出，缓慢的核小体构象波动作为一个潜在的来源，在基因激活动力学的细胞-细胞变异性，他们揭示了多个DNA结合蛋白协同入侵核小体的主导动力学路径。
Nucleosomes sterically occlude their wrapped DNA from interacting with many large protein complexes. How proteins gain access to nucleosomal DNA target sites in vivo is not known. Outer stretches of nucleosomal DNA spontaneously unwrap and rewrap with high frequency, providing rapid and efficient access to regulatory DNA target sites located there; however, rates for access to the nucleosome interior have not been measured. Here we show that for a selected high-affinity nucleosome positioning sequence, the spontaneous DNA unwrapping rate decreases dramatically with distance inside the nucleosome. The rewrapping rate also decreases, but only slightly. Our results explain the previously known strong position dependence on the equilibrium accessibility of nucleosomal DNA, which is characteristic of both selected and natural sequences. Our results point to slow nucleosome conformational fluctuations as a potential source of cell–cell variability in gene activation dynamics, and they reveal the dominant kinetic path by which multiple DNA binding proteins cooperatively invade a nucleosome.