Nuclear proteins bind chromatin to execute and regulate genome-templated processes. While studies of individual nucleosome interactions have suggested that an acidic patch on the nucleosome disk may be a common site for recruitment to chromatin, the pervasiveness of acidic patch binding and whether other nucleosome binding hot-spots exist remain unclear. Here, we use nucleosome affinity proteomics with a library of nucleosomes that disrupts all exposed histone surfaces to comprehensively assess how proteins recognize nucleosomes. We find that the acidic patch and two adjacent surfaces are the primary hot-spots for nucleosome disk interactions, whereas nearly half of the nucleosome disk participates only minimally in protein binding. Our screen defines nucleosome surface requirements of nearly 300 nucleosome interacting proteins implicated in diverse nuclear processes including transcription, DNA damage repair, cell cycle regulation and nuclear architecture. Building from our screen, we demonstrate that the Anaphase-Promoting Complex/Cyclosome directly engages the acidic patch, and we elucidate a redundant mechanism of acidic patch binding by nuclear pore protein ELYS. Overall, our interactome screen illuminates a highly competitive nucleosome binding hub and establishes universal principles of nucleosome recognition.

中文翻译：

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全面的核小体相互作用组筛选建立了核小体结合的基本原理。


核蛋白结合染色质来执行和调节基因组模板过程。虽然对个体核小体相互作用的研究表明，核小体盘上的酸性斑块可能是招募染色质的常见位点，但酸性斑块结合的普遍性以及是否存在其他核小体结合热点仍不清楚。在这里，我们使用核小体亲和蛋白质组学和核小体库来破坏所有暴露的组蛋白表面，以全面评估蛋白质如何识别核小体。我们发现酸性斑块和两个相邻表面是核小体盘相互作用的主要热点，而近一半的核小体盘仅最低限度地参与蛋白质结合。我们的筛选定义了近 300 种核小体相互作用蛋白的核小体表面要求，这些蛋白涉及多种核过程，包括转录、DNA 损伤修复、细胞周期调节和核结构。根据我们的筛选，我们证明了后期促进复合物/环体直接与酸性斑块结合，并且我们阐明了核孔蛋白 ELYS 与酸性斑块结合的冗余机制。总的来说，我们的相互作用组屏幕阐明了高度竞争的核小体结合中心，并建立了核小体识别的通用原则。