Institute of Biological and Chemical Systems, Dept. Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.
Chair of Mathematics in Life Sciences, Dept. Biology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
PLoS Comput Biol. 2021 May 5;17(5):e1008974. doi: 10.1371/journal.pcbi.1008974. eCollection 2021 May.
The genome is packed into the cell nucleus in the form of chromatin. Biochemical approaches have revealed that chromatin is packed within domains, which group into larger domains, and so forth. Such hierarchical packing is equally visible in super-resolution microscopy images of large-scale chromatin organization. While previous work has suggested that chromatin is partitioned into distinct domains via microphase separation, it is unclear how these domains organize into this hierarchical packing. A particular challenge is to find an image analysis approach that fully incorporates such hierarchical packing, so that hypothetical governing mechanisms of euchromatin packing can be compared against the results of such an analysis. Here, we obtain 3D STED super-resolution images from pluripotent zebrafish embryos labeled with improved DNA fluorescence stains, and demonstrate how the hierarchical packing of euchromatin in these images can be described as multiplicative cascades. Multiplicative cascades are an established theoretical concept to describe the placement of ever-smaller structures within bigger structures. Importantly, these cascades can generate artificial image data by applying a single rule again and again, and can be fully specified using only four parameters. Here, we show how the typical patterns of euchromatin organization are reflected in the values of these four parameters. Specifically, we can pinpoint the values required to mimic a microphase-separated state of euchromatin. We suggest that the concept of multiplicative cascades can also be applied to images of other types of chromatin. Here, cascade parameters could serve as test quantities to assess whether microphase separation or other theoretical models accurately reproduce the hierarchical packing of chromatin.
基因组以染色质的形式被包装在细胞核内。生化方法已经揭示，染色质在域内被包装，这些域又分组形成更大的域，依此类推。这种层次化的包装在大尺度染色质组织的超分辨率显微镜图像中同样可见。虽然之前的工作表明，染色质通过微相分离被分割成不同的域，但这些域如何组织成这种层次化的包装尚不清楚。一个特别的挑战是找到一种图像分析方法，该方法充分纳入这种层次化的包装，以便可以将常染色质包装的假设控制机制与这种分析的结果进行比较。在这里，我们从标记有改良 DNA 荧光染料的多能斑马鱼胚胎中获得了 3D STED 超分辨率图像，并展示了这些图像中常染色质的层次化包装如何被描述为乘法级联。乘法级联是一种用来描述越来越小的结构在更大结构内的放置的既定理论概念。重要的是，这些级联可以通过反复应用单个规则来生成人工图像数据，并且仅使用四个参数就可以完全指定。在这里，我们展示了常染色质组织的典型模式是如何反映在这四个参数的值中的。具体来说，我们可以确定模拟常染色质微相分离状态所需的值。我们建议，乘法级联的概念也可以应用于其他类型的染色质图像。在这里，级联参数可以作为测试数量，以评估微相分离或其他理论模型是否准确地再现了染色质的层次化包装。
