Shi Xiangyan, Fedulova Anastasiia S, Kotova Elena Y, Maluchenko Natalya V, Armeev Grigoriy A, Chen Qinming, Prasanna Chinmayi, Sivkina Anastasia L, Feofanov Alexey V, Kirpichnikov Mikhail P, Nordensköld Lars, Shaytan Alexey K, Studitsky Vasily M
Department of Biology, Shenzhen MSU-BIT University, No. 1, International University Park Road, Longgang District, Shenzhen, Guangdong Province 518172, China.
School of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.
Nucleic Acids Res. 2025 Apr 22;53(8). doi: 10.1093/nar/gkaf356.
During various DNA-centered processes in the cell nucleus, the minimal structural units of chromatin organization, nucleosomes, are often transiently converted to hexasomes and tetrasomes missing one or both H2A/H2B histone dimers, respectively. However, the structural and functional properties of the subnucleosomes and their impact on biological processes in the nuclei are poorly understood. Here, using biochemical approaches, molecular dynamics simulations, single-particle Förster resonance energy transfer microscopy, and nuclear magnetic resonance spectroscopy, we have shown that, surprisingly, removal of both dimers from a nucleosome results in much higher mobility of both histones and DNA in the tetrasome. Accordingly, DNase I footprinting shows that DNA-histone interactions in tetrasomes are greatly compromised, resulting in formation of a much lower barrier to transcribing RNA polymerase II than nucleosomes. The data suggest that tetrasomes are remarkably dynamic structures and their formation can strongly affect various biological processes.
在细胞核中以DNA为中心的各种过程中，染色质组织的最小结构单元核小体常常会分别暂时转变为缺失一个或两个H2A/H2B组蛋白二聚体的六体和四体。然而，亚核小体的结构和功能特性及其对细胞核内生物过程的影响却鲜为人知。在此，我们通过生化方法、分子动力学模拟、单粒子Förster共振能量转移显微镜和核磁共振光谱表明，令人惊讶的是，从核小体中去除两个二聚体会导致四体中组蛋白和DNA的流动性大大提高。相应地，DNase I足迹分析表明，四体中的DNA-组蛋白相互作用受到极大损害，与核小体相比，转录RNA聚合酶II的障碍要低得多。数据表明，四体是非常动态的结构，它们的形成会强烈影响各种生物过程。
