Division of Molecular Biology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Martinsried, Germany.
Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Nat Commun. 2021 May 28;12(1):3232. doi: 10.1038/s41467-021-23015-0.
Arrays of regularly spaced nucleosomes dominate chromatin and are often phased by alignment to reference sites like active promoters. How the distances between nucleosomes (spacing), and between phasing sites and nucleosomes are determined remains unclear, and specifically, how ATP-dependent chromatin remodelers impact these features. Here, we used genome-wide reconstitution to probe how Saccharomyces cerevisiae ATP-dependent remodelers generate phased arrays of regularly spaced nucleosomes. We find that remodelers bear a functional element named the 'ruler' that determines spacing and phasing in a remodeler-specific way. We use structure-based mutagenesis to identify and tune the ruler element residing in the Nhp10 and Arp8 modules of the INO80 remodeler complex. Generally, we propose that a remodeler ruler regulates nucleosome sliding direction bias in response to (epi)genetic information. This finally conceptualizes how remodeler-mediated nucleosome dynamics determine stable steady-state nucleosome positioning relative to other nucleosomes, DNA bound factors, DNA ends and DNA sequence elements.
阵列的规则间隔核小体主导染色质，并且经常通过与参考位点（如活跃启动子）对齐来分相。核小体之间的距离（间隔）以及分相位点和核小体之间的距离如何确定仍不清楚，特别是 ATP 依赖性染色质重塑剂如何影响这些特征。在这里，我们使用全基因组重建来探测酿酒酵母 ATP 依赖性重塑剂如何产生规则间隔核小体的分相阵列。我们发现，重塑剂具有一个名为“标尺”的功能元件，该元件以重塑剂特异性的方式决定间隔和分相。我们使用基于结构的诱变来识别和调整位于 INO80 重塑酶复合物的 Nhp10 和 Arp8 模块中的标尺元件。一般来说，我们提出重塑酶标尺调节核小体滑动方向的偏向，以响应（表观）遗传信息。这最终概念化了重塑酶介导的核小体动力学如何相对于其他核小体、DNA 结合因子、DNA 末端和 DNA 序列元件来确定稳定的核小体定位。
