Mesoscale phase separation of chromatin in the nucleus

TL;DR

This study combines imaging and modeling to understand how chromatin organizes within the nucleus, revealing phase separation driven by interactions with the nuclear lamina and volume changes.

Contribution

It introduces a simple polymer model that explains chromatin distribution modes based on self-attraction and lamina binding, aligning with experimental observations.

Findings

Chromatin organization varies with nuclear volume and lamina interactions.

The model reproduces observed chromatin distribution patterns.

Key mechanisms of phase separation are identified through minimal variables.

Abstract

Intact-organism imaging of Drosophila larvae reveals and quantifies chromatin-aqueous phase separation. The chromatin can be organized near the lamina layer of the nuclear envelope, conventionally fill the nucleus, be organized centrally, or as a wetting droplet. These transitions are controlled by changes in nuclear volume and the interaction of chromatin with the lamina (part of the nuclear envelope) at the nuclear periphery. Using a simple polymeric model that includes the key features of chromatin self-attraction and its binding to the lamina, we demonstrate theoretically that it is the competition of these two effects that determines the mode of chromatin distribution. The qualitative trends as well as the compositional profiles obtained in our simulations compare well with the observed intact-organism imaging and quantification. Since the simulations contain only a small number of physical variables we can identify the generic mechanisms underlying the changes in the observed phase separations.