Abstract

Chromatin packing in eukaryotic chromosomes has been traditionally viewed as a hierarchical process, in which nucleosome chains fold into helical chromatin fibers. These fibers would then fold into more complex regular structures. However, recent chromatin imaging studies and analyses of chromosomal DNA contacts within the 3D space of the cell nucleus have necessitated a radical revision of the hierarchical chromatin packing model. According to the new studies, the nucleosome chain has a free spatial configuration without regular helical fibers in most cell types. The overall 3D organization of DNA in the cell nucleus includes chromatin loops and contact domains of up to several million base pairs in size. During cell differentiation, individual structure-functional chromatin domains marked by similar types of histone modifications and functional states can merge together and form chromosomal subcompartments suited for local gene activation or repression. This “attraction of likenesses” may be mediated by direct self-association of nucleosome chains as well as by architectural chromatin proteins making oligomeric protein “bridges” between nucleosomes as well as larger dynamic condensates leading to liquid–liquid phase separation inside the cell nucleus. Future studies of mechanisms of chromatin self-association and compartmentalization will require a combination of molecular, imaging, and computational approaches capable of revealing the 3D organization of the eukaryotic genome with nucleosomal resolution.

中文翻译：

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相似的吸引力：真核染色质的自我关联和区划的机制。

摘要

传统上，真核细胞染色体中的染色质堆积被视为一个分级过程，其中核小体链折叠成螺旋染色质纤维。这些纤维然后将折叠成更复杂的规则结构。但是，最近的染色质成像研究和对细胞核3D空间内染色体DNA接触的分析已经需要对染色质分层堆积模型进行彻底的修改。根据最新研究，在大多数细胞类型中，核小体链具有自由的空间构型，而没有规则的螺旋纤维。DNA在细胞核中的整体3D组织包括染色质环和大小达几百万个碱基对的接触域。在细胞分化过程中 以相似类型的组蛋白修饰和功能状态标记的单个结构功能染色质域可以合并在一起，形成适合局部基因激活或抑制的染色体子小室。这种“相似性的吸引”可通过核小体链的直接自缔合以及建筑染色质蛋白（在核小体之间形成寡聚蛋白“桥”）以及较大的动态缩合物导致细胞核内部液-液相分离来介导。染色质自缔合和区室化机制的未来研究将需要结合分子，成像和计算方法，以揭示具有核小体分辨率的真核基因组的3D组织。