Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, 75005 Paris, France.
Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, the Netherlands.
Mol Cell. 2022 May 5;82(9):1751-1767.e8. doi: 10.1016/j.molcel.2022.02.032. Epub 2022 Mar 22.
Chromosome inheritance depends on centromeres, epigenetically specified regions of chromosomes. While conventional human centromeres are known to be built of long tandem DNA repeats, much of their architecture remains unknown. Using single-molecule techniques such as AFM, nanopores, and optical tweezers, we find that human centromeric DNA exhibits complex DNA folds such as local hairpins. Upon binding to a specific sequence within centromeric regions, the DNA-binding protein CENP-B compacts centromeres by forming pronounced DNA loops between the repeats, which favor inter-chromosomal centromere compaction and clustering. This DNA-loop-mediated organization of centromeric chromatin participates in maintaining centromere position and integrity upon microtubule pulling during mitosis. Our findings emphasize the importance of DNA topology in centromeric regulation and stability.
染色体的遗传取决于着丝粒，这是染色体上的一个特定的表观遗传区域。虽然传统的人类着丝粒已知是由长串联 DNA 重复序列构成的，但它们的大部分结构仍然未知。我们使用单分子技术，如原子力显微镜、纳米孔和光学镊子，发现人类着丝粒 DNA 表现出复杂的 DNA 折叠，如局部发夹。当与着丝粒区域内的特定序列结合时，DNA 结合蛋白 CENP-B 通过在重复序列之间形成明显的 DNA 环来压缩着丝粒，这有利于染色体间着丝粒的紧密化和聚类。这种 DNA 环介导的着丝粒染色质组织参与了在有丝分裂过程中微管牵拉时维持着丝粒位置和完整性。我们的发现强调了 DNA 拓扑结构在着丝粒调控和稳定性中的重要性。
