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.

Highlights

  • The packing of a several meters long genome into a cell nucleus of only a few micrometers diameter is often referenced as a remarkable phenomenon

  • We demonstrate that multiplicative cascades—a concept from theoretical physics used to characterize for example cloud patterns, galaxy locations, or soil patterns—are ideally suited to describe the domainwithin-domain organization of chromatin

  • We have recently addressed the internal patterning of euchromatin in relation to transcription activity, and proposed that a fine-grained pattern of euchromatin domains is established and maintained in line with a microphase-separated state of a microemulsion [16]

Read more

Summary

Introduction

The packing of a several meters long genome into a cell nucleus of only a few micrometers diameter is often referenced as a remarkable phenomenon. In the context of biochemical studies, which investigate genome organization via the point-to-point contacts of different positions on chromosomes, the observation of such hierarchical packing has been explained by the fractal globule model [11,12,13], and more recently by the loop-extrusion model [14, 15]. It is, still poorly understood how the hierarchical domain packing as visualized in microscopy images is established

Objectives
Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call