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

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 highorder 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.

Automated summary

DNA molecules serve as atomic-scale information storage molecules that facilitate reliable information transfer through fault-free repetitions of replications and transcriptions. Despite challenges in observing the three-dimensional structure of chromosomes, nanoscale 3D structures have been successfully obtained using cryogenic coherent X-ray diffraction imaging, revealing the fractal nature of density distributions. Quantitative 3D density maps, supported by molecular dynamics simulations, indicate that internal structures of chromosomes conform to diffusion-limited aggregation behavior, suggesting that 3D chromatin packing occurs through stochastic processes.