Mixed secondary chromatin structure revealed by modeling radiation-induced DNA fragment length distribution
Mixed secondary chromatin structure revealed by modeling radiation-induced DNA fragment length distribution
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DOI：
10.1007/s11427-019-1638-6
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发表时间：
2020-04
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影响因子：
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通讯作者：
Wenzong Ma;Chenyang Gu;Lin Ma;Caoqi Fan;Chao Zhang;Yujie Sun;Cheng Li;Gen Yang
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文献类型：
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作者：
Wenzong Ma;Chenyang Gu;Lin Ma;Caoqi Fan;Chao Zhang;Yujie Sun;Cheng Li;Gen Yang
染色质空间结构在DNA复制、转录、损伤和修复等重要生物学过程中起着重要作用。然而，目前对局部核小体-核小体相互作用形成的染色质二级结构的认识仍存在争议，特别是对于30 nm结构的存在和构象。由于染色质结构影响电离辐射诱导的DNA链断裂的片段长度分布（FLD），因此拟合FLD模式的3D染色质模型可以帮助区分不同的染色质结构模型。在这里，我们开发了一种新的“30-C”模型，将30 nm染色质结构模型与Hi-C数据相结合，该模型测量了基因组中不同基因座之间的空间接触频率。我们首先从Hi-C热图重建25 kb箱的3D坐标。在25 kb箱内，填充了最近研究支持的较低水平的染色质结构。模拟的FLD图案的基础上的30-C模型进行了比较，公布的FLD图案的重离子辐射诱导的模型进行验证。重要的是，30-C模型预测，人类间期成纤维细胞在体内最可能的染色质纤维结构是45%的锯齿形30 nm纤维和55%的10 nm纤维。
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 fibroblastsin vivowas 45% zig-zag 30 nm fibers and 55% 10 nm fibers.