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Abstract

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.
Author summary
DNA is stored inside the cell nucleus in the form of chromatin. Chromatin exhibits a striking three-dimensional organization, where small domains group into larger domains, which again group into larger domains, and so forth. While this hierarchical domain packing is obvious from microscopy images, it is still not entirely clear how it is established, or how it should be properly characterized. Here, we demonstrate that multiplicative cascades-a concept from theoretical physics used to characterize for example cloud patterns, galaxy locations, or soil patterns-are also ideally suited to describe the domain-within-domain organization of chromatin. This description is rather simple, using only four numbers, and can thus facilitate testing of competing theories for the packing of chromatin domains.