Recent research highlights the significance of the three-dimensional structure of chromatin in regulating various cellular processes, particularly transcription. This is achieved through dynamic chromatin structures that facilitate long-range contacts and control spatial accessibility. Chromatin consists of DNA and a variety of proteins, of which histones play an essential structural role by forming nucleosomes. Extensive experimental and theoretical research in recent decades has yielded conflicting results about key factors that regulate the spatial structure of chromatin, which remains enigmatic. By using a computer model that allows us to simulate chromatin volumes containing physiological nucleosome concentrations, we investigated whether nucleosome spacing or nucleosome density is fundamental for three-dimensional chromatin accessibility. Unexpectedly, the regularity of the nucleosome spacing is crucial for determining the accessibility of the chromatin network to diffusive processes, whereas variation in nucleosome concentrations has only minor effects. Using only the basic physical properties of DNA and nucleosomes was sufficient to generate chromatin structures consistent with published electron microscopy data. Contrary to other work, we found that nucleosome density did not substantially alter the properties of chromatin fibers or contact probabilities of genomic loci. No breakup of fiber-like structures was observed at high molar density. These findings challenge previous assumptions and highlight the importance of nucleosome spacing as a key driver of chromatin organization. These results identified changes in nucleosome spacing as a tentative mechanism for altering the spatial chromatin structure and thus genomic functions.

中文翻译：

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核小体间距控制染色质空间结构和可及性

最近的研究强调了染色质的三维结构在调节各种细胞过程（特别是转录）中的重要性。这是通过促进远距离接触并控制空间可及性的动态染色质结构来实现的。染色质由 DNA 和多种蛋白质组成，其中组蛋白通过形成核小体发挥重要的结构作用。近几十年来，广泛的实验和理论研究对于调节染色质空间结构的关键因素产生了相互矛盾的结果，这仍然是一个谜。通过使用允许我们模拟包含生理核小体浓度的染色质体积的计算机模型，我们研究了核小体间距或核小体密度是否是三维染色质可及性的基础。出乎意料的是，核小体间距的规律性对于确定染色质网络对扩散过程的可及性至关重要，而核小体浓度的变化只有很小的影响。仅使用 DNA 和核小体的基本物理特性就足以生成与已发表的电子显微镜数据一致的染色质结构。与其他工作相反，我们发现核小体密度并没有显着改变染色质纤维的特性或基因组位点的接触概率。在高摩尔密度下没有观察到纤维状结构的破裂。这些发现挑战了之前的假设，并强调了核小体间距作为染色质组织关键驱动因素的重要性。这些结果确定核小体间距的变化是改变空间染色质结构并从而改变基因组功能的初步机制。