School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, 2006, Australia.
Molecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.
Nat Commun. 2020 Mar 23;11(1):1519. doi: 10.1038/s41467-020-15183-2.
Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. The mechanism, however, is only partially resolved, and it is unclear if it is conserved among the four remodeller families. Here we use single-molecule assays to examine the mechanism of action of CHD4, which is part of the least well understood family. We demonstrate that the binding energy for CHD4-nucleosome complex formation-even in the absence of nucleotide-triggers significant conformational changes in DNA at the entry side, effectively priming the system for remodelling. During remodelling, flanking DNA enters the nucleosome in a continuous, gradual manner but exits in concerted 4-6 base-pair steps. This decoupling of entry- and exit-side translocation suggests that ATP-driven movement of entry-side DNA builds up strain inside the nucleosome that is subsequently released at the exit side by DNA expulsion. Based on our work and previous studies, we propose a mechanism for nucleosome sliding.
染色质重塑酶通过水解 ATP 将核小体 DNA 逆着组蛋白八聚体移动。然而，其机制尚未完全解决，并且不清楚它是否在四个重塑酶家族中都保守。在这里，我们使用单分子测定法来研究 CHD4 的作用机制，CHD4 是了解最少的家族的一部分。我们证明，即使在没有核苷酸的情况下，CHD4-核小体复合物形成的结合能也会引发入口侧 DNA 的显著构象变化，从而有效地为重塑系统做好准备。在重塑过程中，侧翼 DNA 以连续、渐进的方式进入核小体，但以协调的 4-6 个碱基对的步长退出。这种进入侧和退出侧转运的解耦表明，ATP 驱动的进入侧 DNA 的移动在内核小体内部产生应变，随后通过 DNA 排出在出口侧释放。基于我们的工作和以前的研究，我们提出了核小体滑动的机制。
Zotero 插件
