Recent studies have implicated the nucleosome acidic patch in the activity of ATP-dependent chromatin remodeling machines. We used a photocrosslinking-based nucleosome profiling technology (photoscanning) to identify a conserved basic motif within the catalytic subunit of ISWI remodelers, SNF2h, which engages this nucleosomal epitope. This region of SNF2h is essential for chromatin remodeling activity in a reconstituted biochemical system and in cells. Our studies suggest that the basic motif in SNF2h plays a critical role in anchoring the remodeler to the nucleosomal surface. We also examine the functional consequences of several cancer-associated histone mutations that map to the nucleosome acidic patch. Kinetic studies using physiologically relevant heterotypic nucleosomal substrates ('Janus' nucleosomes) indicate that these cancer-associated mutations can disrupt regularly spaced chromatin structure by inducing ISWI-mediated unidirectional nucleosome sliding. These results indicate a potential mechanistic link between oncogenic histones and alterations to the chromatin landscape.

中文翻译：

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将 ISWI 锚定到核小体酸性斑块上的基本基序调节核小体间距。

最近的研究表明核小体酸性斑块与 ATP 依赖性染色质重塑机器的活性有关。我们使用基于光交联的核小体分析技术（光扫描）来识别 ISWI 重塑剂催化亚基 SNF2h 内的保守基本基序，该基序与该核小体表位结合。SNF2h 的这个区域对于重建的生化系统和细胞中的染色质重塑活性至关重要。我们的研究表明，SNF2h 中的基本基序在将重塑因子锚定到核小体表面方面发挥着关键作用。我们还检查了几种与癌症相关的组蛋白突变映射到核小体酸性斑块的功能后果。使用生理相关异型核小体底物（“Janus”核小体）的动力学研究表明，这些与癌症相关的突变可以通过诱导 ISWI 介导的单向核小体滑动来破坏规则间隔的染色质结构。这些结果表明致癌组蛋白与染色质景观改变之间存在潜在的机制联系。