Dias Juliana Kikumoto, D'Arcy Sheena
Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas, 75080, USA.
Biochem Soc Trans. 2025 Jan 31;53(1):BCJ20240452. doi: 10.1042/BST20230721.
Nucleosomes, the building block of chromatin, are responsible for regulating access to the DNA sequence. This control is critical for essential cellular processes, including transcription and DNA replication and repair. Studying chromatin can be challenging both in vitro and in vivo, leading many to use a mono-nucleosome system to answer fundamental questions relating to chromatin regulators and binding partners. However, the mono-nucleosome fails to capture essential features of the chromatin structure, such as higher-order chromatin folding, local nucleosome-nucleosome interactions, and linker DNA trajectory and flexibility. We briefly review significant discoveries enabled by the mono-nucleosome and emphasize the need to go beyond this model system in vitro. Di-, tri-, and tetra-nucleosome arrays can answer important questions about chromatin folding, function, and dynamics. These multi-nucleosome arrays have highlighted the effects of varying linker DNA lengths, binding partners, and histone post-translational modifications in a more chromatin-like environment. We identify various chromatin regulatory mechanisms yet to be explored with multi-nucleosome arrays. Combined with in-solution biophysical techniques, studies of minimal multi-nucleosome chromatin models are feasible.
核小体是染色质的基本组成单位，负责调控对DNA序列的访问。这种控制对于包括转录、DNA复制和修复在内的基本细胞过程至关重要。在体外和体内研究染色质都具有挑战性，这使得许多人使用单核小体系统来回答与染色质调节因子和结合伴侣相关的基本问题。然而，单核小体无法捕捉染色质结构的基本特征，如高阶染色质折叠、局部核小体-核小体相互作用以及连接DNA的轨迹和灵活性。我们简要回顾了单核小体带来的重大发现，并强调了在体外超越这个模型系统的必要性。双核小体、三核小体和四核小体阵列可以回答有关染色质折叠、功能和动力学的重要问题。这些多核小体阵列在更类似染色质的环境中突出了不同连接DNA长度、结合伴侣和组蛋白翻译后修饰的影响。我们确定了各种尚未用多核小体阵列探索的染色质调节机制。结合溶液中的生物物理技术，对最小多核小体染色质模型的研究是可行的。
