Chen Lifeng, Maristany M Julia, Farr Stephen E, Luo Jinyue, Gibson Bryan A, Doolittle Lynda K, Espinosa Jorge R, Huertas Jan, Redding Sy, Collepardo-Guevara Rosana, Rosen Michael K
Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Marine Biological Laboratory Chromatin Collaborative, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
bioRxiv. 2024 Dec 23:2024.12.23.627571. doi: 10.1101/2024.12.23.627571.
Cellular chromatin displays heterogeneous structure and dynamics, properties that control diverse nuclear processes. Models invoke phase separation of conformational ensembles of chromatin fibers as a mechanism regulating chromatin organization . Here we combine biochemistry and molecular dynamics simulations to examine, at single base-pair resolution, how nucleosome spacing controls chromatin phase separation. We show that as DNA linkers extend from 25 bp to 30 bp, as examplars of 10N+5 and 10N (integer N) bp lengths, chromatin condensates become less thermodynamically stable and nucleosome mobility increases. Simulations reveal that this is due to trade-offs between inter- and intramolecular nucleosome stacking, favored by rigid 10N+5 and 10N bp linkers, respectively. A remodeler can induce or inhibit phase separation by moving nucleosomes, changing the balance between intra- and intermolecular stacking. The intrinsic phase separation capacity of chromatin enables fine tuning of compaction and dynamics, likely contributing to heterogeneous chromatin organization .
细胞染色质呈现出异质性的结构和动力学，这些特性控制着多种核过程。模型认为染色质纤维构象集合的相分离是调节染色质组织的一种机制。在这里，我们结合生物化学和分子动力学模拟，以单碱基对分辨率研究核小体间距如何控制染色质相分离。我们发现，作为10N + 5和10N（整数N）碱基对长度的示例，当DNA连接子从25 bp延伸到30 bp时，染色质凝聚物的热力学稳定性降低，核小体流动性增加。模拟表明，这是由于分子间和分子内核小体堆积之间的权衡，分别受刚性10N + 5和10N碱基对连接子的青睐。重塑因子可以通过移动核小体来诱导或抑制相分离，改变分子内和分子间堆积之间的平衡。染色质的内在相分离能力能够对压缩和动力学进行微调，这可能有助于形成异质性染色质组织。
