Department of Physics-Laboratory of Atomic and Solid State Physics, Cornell University, Ithaca, New York 14853, USA.
Howard Hughes Medical Institute, Cornell University, Ithaca, New York 14853, USA.
Nat Commun. 2016 Nov 3;7:13337. doi: 10.1038/ncomms13337.
Proper cell function requires preservation of the spatial organization of chromatin modifications. Maintenance of this epigenetic landscape necessitates the transfer of parental nucleosomes to newly replicated DNA, a process that is stringently regulated and intrinsically linked to replication fork dynamics. This creates a formidable setting from which to isolate the central mechanism of transfer. Here we utilized a minimal experimental system to track the fate of a single nucleosome following its displacement, and examined whether DNA mechanics itself, in the absence of any chaperones or assembly factors, may serve as a platform for the transfer process. We found that the nucleosome is passively transferred to available dsDNA as predicted by a simple physical model of DNA loop formation. These results demonstrate a fundamental role for DNA mechanics in mediating nucleosome transfer and preserving epigenetic integrity during replication.
细胞的正常功能需要维持染色质修饰的空间组织。为了保持这种表观遗传景观，需要将亲本核小体转移到新复制的 DNA 上，这个过程受到严格的调控，并且与复制叉动力学密切相关。这就为分离转移的核心机制带来了巨大的挑战。在这里，我们利用一个最小的实验系统来跟踪单个核小体在被置换后的命运，并研究在没有任何伴侣蛋白或组装因子的情况下，DNA 力学本身是否可以作为转移过程的平台。我们发现，核小体如简单的 DNA 环形成物理模型所预测的那样，被被动地转移到可用的双链 DNA 上。这些结果表明 DNA 力学在介导核小体转移和在复制过程中维持表观遗传完整性方面起着基础性的作用。
