Stochastic chromatin packing of 3D mitotic chromosomes revealed by coherent X-rays

相干X射线揭示的3D有丝分裂染色体的随机染色质堆积

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作者:Daeho Sung, Chan Lim, Masatoshi Takagi, Chulho Jung, Heemin Lee, Do Hyung Cho, Jae-Yong Shin, Kangwoo Ahn, Junha Hwang, Daewoong Nam, Yoshiki Kohmura, Tetsuya Ishikawa, Do Young Noh, Naoko Imamoto, Jae-Hyung Jeon, Changyong Song

Abstract

DNA molecules are atomic-scale information storage molecules that promote reliable information transfer via fault-free repetitions of replications and transcriptions. Remarkable accuracy of compacting a few-meters-long DNA into a micrometer-scale object, and the reverse, makes the chromosome one of the most intriguing structures from both physical and biological viewpoints. However, its three-dimensional (3D) structure remains elusive with challenges in observing native structures of specimens at tens-of-nanometers resolution. Here, using cryogenic coherent X-ray diffraction imaging, we succeeded in obtaining nanoscale 3D structures of metaphase chromosomes that exhibited a random distribution of electron density without characteristics of high-order folding structures. Scaling analysis of the chromosomes, compared with a model structure having the same density profile as the experimental results, has discovered the fractal nature of density distributions. Quantitative 3D density maps, corroborated by molecular dynamics simulations, reveal that internal structures of chromosomes conform to diffusion-limited aggregation behavior, which indicates that 3D chromatin packing occurs via stochastic processes.

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