Conformational and Interaction Landscape of Histone H4 Tails in Nucleosomes Probed by Paramagnetic NMR Spectroscopy.
Conformational and Interaction Landscape of Histone H4 Tails in Nucleosomes Probed by Paramagnetic NMR Spectroscopy.
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DOI：
10.1021/jacs.3c10340
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发表时间：
2023-11
影响因子：
15
通讯作者：
Wenjun Sun;O. O. Lebedenko-O.;Nicole Gonzalez Salguero;Matthew D. Shannon;Mohamad Zandian;Michael G. Poirier;N. Skrynnikov;C. Jaroniec
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文献类型：
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作者：
Wenjun Sun;O. O. Lebedenko-O.;Nicole Gonzalez Salguero;Matthew D. Shannon;Mohamad Zandian;Michael G. Poirier;N. Skrynnikov;C. Jaroniec
染色质的基本重复单位核小体由大约147个碱基对的双链DNA和组蛋白八聚体组成，组蛋白八聚体含有两个拷贝的组蛋白H2 A、H2 B、H3和H4。每个组蛋白都具有一个动态无序的N-末端尾部结构域，并且已经确定组蛋白H3和H4的尾部在染色质致密化和调节中起关键作用。在这里，我们调查的构象合奏和相互作用的H4尾巴在核小体的顺磁弛豫增强（PREs）的重组样品重构与15 N-富集的H4和氮氧自旋标记H3的溶液NMR测量的装置。实验PREs，其中报告的接近个别H4尾残基的不同H3自旋标记位点，解释通过使用微秒时间尺度的分子动力学模拟的核小体核心颗粒。总的来说，这些数据能够改善组蛋白H4尾在核小体中的定位，并支持H4尾与核小体DNA进行模糊复杂相互作用的观点。
The fundamental repeat unit of chromatin, the nucleosome, consists of approximately 147 base pairs of double-stranded DNA and a histone protein octamer containing two copies each of histones H2A, H2B, H3, and H4. Each histone possesses a dynamically disordered N-terminal tail domain, and it is well-established that the tails of histones H3 and H4 play key roles in chromatin compaction and regulation. Here we investigate the conformational ensemble and interactions of the H4 tail in nucleosomes by means of solution NMR measurements of paramagnetic relaxation enhancements (PREs) in recombinant samples reconstituted with 15N-enriched H4 and nitroxide spin-label tagged H3. The experimental PREs, which report on the proximities of individual H4 tail residues to the different H3 spin-label sites, are interpreted by using microsecond time-scale molecular dynamics simulations of the nucleosome core particle. Collectively, these data enable improved localization of histone H4 tails in nucleosomes and support the notion that H4 tails engage in a fuzzy complex interaction with nucleosomal DNA.