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Mixed secondary chromatin structure revealed by modeling radiation-induced DNA fragment length distribution

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Abstract

Spatial chromatin structure plays fundamental roles in many vital biological processes including DNA replication, transcription, damage and repair. However, the current understanding of the secondary structure of chromatin formed by local nucleosome-nucleosome interactions remains controversial, especially for the existence and conformation of 30 nm structure. Since chromatin structure influences the fragment length distribution (FLD) of ionizing radiation-induced DNA strand breaks, a 3D chromatin model fitting FLD patterns can help to distinguish different models of chromatin structure. Here, we developed a novel “30-C” model combining 30 nm chromatin structure models with Hi-C data, which measured the spatial contact frequency between different loci in the genome. We first reconstructed the 3D coordinates of the 25 kb bins from Hi-C heatmaps. Within the 25 kb bins, lower level chromatin structures supported by recent studies were filled. Simulated FLD patterns based on the 30-C model were compared to published FLD patterns induced by heavy ion radiation to validate the models. Importantly, the 30-C model predicted that the most probable chromatin fiber structure for human interphase fibroblasts in vivo was 45% zig-zag 30 nm fibers and 55% 10 nm fibers.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (11875079 and 11434001). C.L. was supported by NSFC (31871266), the National Key Research and Development Project of China (2016YFA0100103), and NSFC Key Research Grant 71532001.

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Authors and Affiliations

  1. State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, 100871, China

    Wenzong Ma, Chenyang Gu, Lin Ma & Gen Yang

  2. Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan

    Chenyang Gu

  3. Medical Artificial Intelligence and Automation, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Lin Ma

  4. Center for Bioinformatics, School of Life Sciences and Center for Statistical Science, Peking University, Beijing, 100871, China

    Caoqi Fan, Chao Zhang & Cheng Li

  5. State Key Laboratory of Membrane Biology, School of Life Sciences, and Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, 100871, China

    Yujie Sun

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  1. Wenzong Ma
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  2. Chenyang Gu
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  3. Lin Ma
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Correspondence to Cheng Li or Gen Yang.

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Ma, W., Gu, C., Ma, L. et al. Mixed secondary chromatin structure revealed by modeling radiation-induced DNA fragment length distribution. Sci. China Life Sci. 63, 825–834 (2020). https://doi.org/10.1007/s11427-019-1638-6

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