Structural implications of combinatorial interactions within subnucleosomes

Chromatin organizes genomic DNA into a dynamic, compact structure that regulates the genome's accessibility and stability. A increasing amount of research suggests that subnucleosomal particles serve as crucial structural intermediates during chromatin assembly, remodeling, and centromere maintenance, despite the nucleosome general acceptance as the fundamental repeating unit of chromatin. H3:H4and CENP-A:H4 complexes create tetrameric subnucleosome structures that are crucial for nucleosome assembly and for creating the unique centromeric chromatin architecture. Under different physiological conditions, these particles can affect chromatin stability, histone–DNA interactions, and DNA wrapping. By altering the electrostatic interactions between DNA and histone proteins and by maintaining higher-order chromatin structures, divalent cations like Mg²⁺ are known to control chromatin compaction. Nevertheless, limited is referred to about how Mg²⁺ influences the stability and structural dynamics of subnucleosomal structures. In this study, we use atomistic molecular dynamics simulations to study the conformational dynamics and structural characteristics of H3:H4 and CENP-A:H4 subnucleosomes, as well as how Mg²⁺ ions affect their overall structural organization, stability, and interaction patterns.染色质（Chromatin）将基因组DNA组装为动态紧凑的结构，以此调控基因组的可及性与稳定性。尽管核小体（Nucleosome）已被普遍认为是染色质的基本重复单元，但越来越多的研究表明，亚核小体颗粒在染色质组装、重塑以及着丝粒维持过程中发挥着关键的结构中介作用。H3:H4与CENP-A:H4复合物可形成四聚体亚核小体结构，这对于核小体组装以及构建独特的着丝粒染色质架构至关重要。在不同生理条件下，这类颗粒可影响染色质稳定性、组蛋白-DNA相互作用以及DNA缠绕程度。众所周知，二价阳离子（如Mg²⁺）可通过改变DNA与组蛋白之间的静电相互作用，并维持高阶染色质结构，从而调控染色质压缩。然而，目前关于Mg²⁺如何影响亚核小体结构的稳定性与结构动态的相关研究仍较为匮乏。本研究采用全原子分子动力学模拟，探究了H3:H4与CENP-A:H4亚核小体的构象动态与结构特征，以及Mg²⁺离子对其整体结构组织、稳定性和相互作用模式的影响。