Theoretical study of chromatin organization at the mesoscale

Recent experiments on chromatin of muscle nuclei in intact organisms, have shown that chromatin may organize peripherally with chromatin depleted regions in the center of the nucleus, challenging the conventional picture in which chromatin fills the entire nuclear envelope. Furthermore, polymer simulations offer a plausible explanation for such chromatin organization, suggesting that it stems from an interplay between chromatin self-attraction and its interactions with the nuclear lamina (NL) via the lamin-associated domains (LAD) of the chromatin. Motivated by these findings, we provide analytical insight using two complementary approaches. On the one hand, we predict the chromatin concentration profiles using a mean-field polymer model in which we account for the bonding interaction between LAD and the NL. On the other hand, we model chromatin as a liquid droplet and study the transitions between different types of chromatin organization at the mesoscale as a function of the droplet surface tension, the LAD fraction of the chromatin, and their interaction strength with the NL. Comparison of our analytical predictions with Brownian dynamical simulations, demonstrate the roles of surface tension and the lamina interaction in determining the nuclear-scale chromatin organization.