PHF1 Tudor and N-terminal domains synergistically target partially unwrapped nucleosomes to increase DNA accessibility.
PHF1 Tudor and N-terminal domains synergistically target partially unwrapped nucleosomes to increase DNA accessibility.
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DOI：
10.1093/nar/gkw1320
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发表时间：
2017-04-20
影响因子：
14.9
通讯作者：
Poirier MG
中科院分区：
文献类型：
--
作者：
Gibson MD;Gatchalian J;Slater A;Kutateladze TG;Poirier MG
人PHF 1的Tudor结构域识别组蛋白H3上的三甲基化赖氨酸36（H3 K36 me 3）。PHF 1依赖于这种相互作用来调节PRC 2甲基转移酶活性，定位于DNA双链断裂并介导核小体可及性。在这里，我们调查的PHF 1 N-末端结构域（NTD）的Tudor结构域与核小体的相互作用的影响。我们表明，当NTD原生连接到Tudor域时，它是部分有序的。通过FRET和单分子研究的组合，我们发现，增加的DNA可及性内的H3 K36 me 3-含有核小体，煽动的Tudor结合到H3 K36 me 3，是显着增强的NTD。我们证明，这几乎是数量级的增加是由于优先结合PHF 1部分解开核小体，PHF 1改变DNA-蛋白质结合的核小体内，通过降低解离速率。这些结果突出了PTM结合蛋白调节DNA可及性的效力，并强调了核小体通过增加蛋白质解离速率来控制DNA-蛋白质结合的新机制的作用。
The Tudor domain of human PHF1 recognizes trimethylated lysine 36 on histone H3 (H3K36me3). PHF1 relies on this interaction to regulate PRC2 methyltransferase activity, localize to DNA double strand breaks and mediate nucleosome accessibility. Here, we investigate the impact of the PHF1 N-terminal domain (NTD) on the Tudor domain interaction with the nucleosome. We show that the NTD is partially ordered when it is natively attached to the Tudor domain. Through a combination of FRET and single molecule studies, we find that the increase of DNA accessibility within the H3K36me3-containing nucleosome, instigated by the Tudor binding to H3K36me3, is dramatically enhanced by the NTD. We demonstrate that this nearly order of magnitude increase is due to preferential binding of PHF1 to partially unwrapped nucleosomes, and that PHF1 alters DNA–protein binding within the nucleosome by decreasing dissociation rates. These results highlight the potency of a PTM-binding protein to regulate DNA accessibility and underscores the role of the novel mechanism by which nucleosomes control DNA–protein binding through increasing protein dissociation rates.