Zhang Ling, Xie Wen Jun, Liu Sirui, Meng Luming, Gu Chan, Gao Yi Qin
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China; Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China.
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Biophys J. 2017 Oct 3;113(7):1395-1404. doi: 10.1016/j.bpj.2017.08.019.
The relationship between DNA methylation and chromatin structure is still largely unknown. By analyzing a large set of published sequencing data, we observed a long-range power law correlation of DNA methylation with cell class-specific scaling exponents in the range of tens of kilobases. We showed that such cell class-specific scaling exponents are caused by different patchiness of DNA methylation in different cells. By modeling the chromatin structure using high-resolution chromosome conformation capture data and mapping the methylation level onto the modeled structure, we demonstrated that the patchiness of DNA methylation is related to chromatin structure. The scaling exponents of the power law correlation are thus a display of the spatial organization of chromatin. Besides the long-range correlation, we also showed that the local correlation of DNA methylation is associated with nucleosome positioning. The local correlation of partially methylated domains is different from that of nonpartially methylated domains, suggesting that their chromatin structures differ at the scale of several hundred base pairs (covering a few nucleosomes). Our study provides a novel, to our knowledge, view of the spatial organization of chromatin structure from a perspective of DNA methylation, in which both long-range and local correlations of DNA methylation along the genome reflect the spatial organization of chromatin.
DNA甲基化与染色质结构之间的关系在很大程度上仍然未知。通过分析大量已发表的测序数据，我们观察到DNA甲基化与细胞类别特异性缩放指数在数十千碱基范围内存在长程幂律相关性。我们表明，这种细胞类别特异性缩放指数是由不同细胞中DNA甲基化的不同斑驳程度引起的。通过使用高分辨率染色体构象捕获数据对染色质结构进行建模，并将甲基化水平映射到建模结构上，我们证明了DNA甲基化的斑驳程度与染色质结构有关。因此，幂律相关性的缩放指数是染色质空间组织的一种表现。除了长程相关性外，我们还表明DNA甲基化的局部相关性与核小体定位有关。部分甲基化结构域的局部相关性与非部分甲基化结构域的不同，这表明它们的染色质结构在几百个碱基对（覆盖几个核小体）的尺度上存在差异。据我们所知，我们的研究从DNA甲基化的角度为染色质结构的空间组织提供了一种新颖的观点，其中沿着基因组的DNA甲基化的长程和局部相关性都反映了染色质的空间组织。
