Regulation of chromatin microphase separation by adsorbed protein complexes

Abstract

We show evidence of the association of RNA Polymerase II (RNAP) with chromatin in a core-shell organization, reminiscent of microphase separation where the cores comprise dense chromatin and the shell, RNAP and chromatin with low density. These observations motivate our physical model for the regulation of core-shell chromatin organization. Here, we model chromatin as a multiblock copolymer, comprising active and inactive regions (blocks) that are both in poor solvent and tend to be condensed in the absence of binding proteins. However, we show that the solvent quality for the active regions of chromatin can be regulated by the binding of protein complexes (e.g. RNAP). Using the theory of polymer brushes, we find that such binding leads to swelling of the active chromatin regions which in turn, modifies the spatial organization of the inactive regions. In addition, we use simulations to study spherical chromatin micelles, whose cores comprise inactive regions and shells comprise active regions and bound protein complexes. In spherical micelles the swelling increases the number of inactive cores and controls their size. Thus, genetic modifications affecting the binding strength of chromatin-binding protein complexes may modulate the solvent quality experienced by chromatin and regulate the physical organization of the genome.

The LINC Complex Inhibits Excessive Chromatin Repression

“…A detailed description of the dynamic harmonic potential (bonding/unbonding) can be found in Refs. [ 35 , 38 ]. We used the LAMMPS molecular dynamics package to simulate our model system [ 39 ].…”

Nucleo-cytoplasmic environment modulates spatio-temporal p53 phase separation

“…Previous study also suggests that nucleic acids modulate the formation of multicomponent LLPS and material property of the condensates 23,104,127 . Our data thus suggests that upon entry into the nucleus, p53 readily undergoes LLPS into a micro-phase separated condensate state 79,128 in the presence of nucleic acid, which might act as a ready pool of functional p53. This process might help p53 to stay in the vicinity of specific DNA (upon exposure) 129 , which subsequently may get dissolved into a soluble state for performing the tumor suppressor/transcriptional activity.…”

The LINC complex inhibits excessive chromatin repression

“…A detailed description of the dynamic harmonic potential (bonding/unbonding) can be found in Refs. (Bajpai et al, 2021; Adame-Arana et al, 2022). We used the LAMMPS molecular dynamics package to simulate our model system (Plimpton, 1995).…”