High-resolution and high-accuracy topographic and transcriptional maps of the nucleosome barrier
High-resolution and high-accuracy topographic and transcriptional maps of the nucleosome barrier
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DOI：
10.7554/elife.48281
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发表时间：
2019-07-31
期刊：
影响因子：
7.7
通讯作者：
Bustamante, Carlos
中科院分区：
文献类型：
--
作者：
Chen, Zhijie;Gabizon, Ronen;Bustamante, Carlos
核小体代表RNA聚合酶II（Pol II）在转录过程中必须克服的机械和能量障碍。一个高分辨率的描述的障碍地形，其调制表观遗传修饰，以及它们对波尔II核小体交叉动力学的影响，仍然失踪。在这里，我们获得地形和转录（Pol II停留时间）地图的典型，H2A.Z，和monoubiquitinated H2B（uH2B）核小体在近碱基对的分辨率和准确性。Pol II交叉动力学是复杂的，显示在特定位点的停顿，回溯，和包裹状态之间的核小体跳跃。虽然H2A.Z加宽了屏障，但uH2B提高了屏障，这两种修饰都大大延长了Pol II的穿越时间。使用在每个核小体位置的Pol II的停留时间，我们提取的障碍的能量。H2A.Z和uH2B的正交屏障修饰及其对Pol II动力学的影响使其在+1核小体中观察到的富集合理化，并提出了选择性控制基因表达的机制。
Nucleosomes represent mechanical and energetic barriers that RNA Polymerase II (Pol II) must overcome during transcription. A high-resolution description of the barrier topography, its modulation by epigenetic modifications, and their effects on Pol II nucleosome crossing dynamics, is still missing. Here, we obtain topographic and transcriptional (Pol II residence time) maps of canonical, H2A.Z, and monoubiquitinated H2B (uH2B) nucleosomes at near base-pair resolution and accuracy. Pol II crossing dynamics are complex, displaying pauses at specific loci, backtracking, and nucleosome hopping between wrapped states. While H2A.Z widens the barrier, uH2B heightens it, and both modifications greatly lengthen Pol II crossing time. Using the dwell times of Pol II at each nucleosomal position we extract the energetics of the barrier. The orthogonal barrier modifications of H2A.Z and uH2B, and their effects on Pol II dynamics rationalize their observed enrichment in +1 nucleosomes and suggest a mechanism for selective control of gene expression.