Department of Biotechnology, School of Biological Sciences, University of Kashmir, Srinagar, J&K, 190006, India.
Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark.
Sci Adv. 2024 Jun 7;10(23):eadn2955. doi: 10.1126/sciadv.adn2955.
The hierarchical chromatin organization begins with formation of nucleosomes, which fold into chromatin domains punctuated by boundaries and ultimately chromosomes. In a hierarchal organization, lower levels shape higher levels. However, the dependence of higher-order 3D chromatin organization on the nucleosome-level organization has not been studied in cells. We investigated the relationship between nucleosome-level organization and higher-order chromatin organization by perturbing nucleosomes across the genome by deleting () and () chromatin remodeling factors in budding yeast. We find that changes in nucleosome-level properties are accompanied by changes in 3D chromatin organization. Short-range chromatin contacts up to a few kilo-base pairs decrease, chromatin domains weaken, and boundary strength decreases. Boundary strength scales with accessibility and moderately with width of nucleosome-depleted region. Change in nucleosome positioning seems to alter the stiffness of chromatin, which can affect formation of chromatin contacts. Our results suggest a biomechanical "bottom-up" mechanism by which nucleosome distribution across genome shapes 3D chromatin organization.
分层染色质组织始于核小体的形成,核小体折叠成染色质域,由边界打断,最终形成染色体。在分层组织中,较低层次塑造较高层次。然而,在细胞中,尚未研究高阶 3D 染色质组织对核小体水平组织的依赖性。我们通过删除芽殖酵母中 () 和 () 染色质重塑因子,在整个基因组中扰动核小体,研究了核小体水平组织与高阶染色质组织之间的关系。我们发现,核小体水平特性的变化伴随着 3D 染色质组织的变化。短程染色质接触减少到几千个碱基对,染色质域减弱,边界强度降低。边界强度与可及性呈中等程度相关,与核小体缺失区域的宽度呈中等程度相关。核小体定位的变化似乎改变了染色质的刚性,这可能会影响染色质接触的形成。我们的结果表明,一种基于生物力学的“自下而上”的机制,即基因组中核小体的分布决定了 3D 染色质组织。