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 composition 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.
Highlights
Chromatin is a complex, linear macromolecule comprising DNA and histone proteins which in eukaryotic cells, is localized in the nucleus where it is solubilized in water, salts, and other small molecules (Cooper and Hausman, 2000; Phillips et al, 2012)
Even the conventional picture accounts for phase separation similar to that of soluble AB block copolymers (Rubinstein and Colby, 2003), with regions of transcriptionally active euchromatin (A block) separated from regions of relatively inactive heterochromatin (B block); both are assumed to be homogeneously solubilized in the aqueous phase (Erdel and Rippe, 2018; Narlikar, 2020; Strom et al, 2017; Larson et al, 2017)
We summarize the results of the Brownian dynamics simulations and discuss how conventional, peripheral and central organization of chromatin can be achieved by changing hydration, chromatin-lamina interactions, and intra-chromatin interactions
Summary
Linear macromolecule comprising DNA and histone proteins which in eukaryotic cells, is localized in the nucleus where it is solubilized in water, salts, and other small molecules (Cooper and Hausman, 2000; Phillips et al, 2012). Another study observed a larger scale phase separation of chromatin and the aqueous phase in early development, with the chromatin localized to the nuclear periphery (Popken et al, 2014). We have presented (see Appendix 1—figure 1) intact-organism imaging of Drosophila larvae nuclei where the chromatin was labeled by H2B-RFP, and the nuclear envelope was labeled by Nesprin/Klar-GFP. These experiments reveal and quantify chromatin-aqueous phase separation and its control by changes in the nuclear volume and the interaction of chromatin with the lamina (part of the nuclear envelope) at the nuclear periphery (Amiad-Pavlov et al, 2020). We demonstrate theoretically that it is the competition of these two effects, together with the self-attraction of the chromatin to itself that
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