Fig. 6: Polymer simulations of chromosomes demonstrate how loop extrusion, interaction energy and polymer properties may govern microcompartmentalization throughout the M-to-G1 transition.
From: Dynamics of microcompartment formation at the mitosis-to-G1 transition
a, Illustrations of key components of the simulation model. Top left, condensins I and II (green and turquoise, respectively) dynamically bind and unbind to the chromatin fiber (gray) and extrude chromatin polymer loops. Condensin I has a relatively short residence time, τres, which results in the formation of small loops nested within large loops formed by condensin II. Top right, cohesin (yellow) extrudes loops and may stop when it encounters correctly oriented CTCF (black arrowheads). Bottom left, the chromatin fiber is a block copolymer with three types of blocks, which self-interact with affinities given by the interaction energies, 𝜖i. Bottom right, the Dag1 region (colored) is simulated as part of a larger polymer chromosome (gray), which is confined to a sphere. b,c, Contact maps from steady-state simulations of the Dag1 region for different loop extruder residence times, τres (decreasing from left to right columns), and microcompartmentalization affinities, 𝜖C (decreasing from top to bottom rows; b), or different polymer volumetric densities, ρchr (decreasing from top to bottom; c). Linear density of loop extruders, 1/d, was fixed at one extruder per 100 kb in these simulations. Small gray boxes denote regions magnified in insets. d, Summary of simulation model of chromosome organization throughout the M-to-G1 transition. Lines show the linear densities of condensins I and II and cohesin, as well as a 2.6-fold decrease in polymer density through the M-to-G1 transition. Gray regions indicate the time during which data were collected for annotated cell-cycle phases. The red region indicates initial equilibration of the simulation modeling PM arrest, as further described in the text. e, Bottom, contact maps from various times in the M-to-G1 transition simulations with corresponding simulation snapshots (bottom). The middle row displays zoomed-in views of the region indicated in the top row. Insets within this row show the 40-kb × 40-kb region of the contact map indicated by the small black box, showing the dynamics of microcompartmental contacts throughout the transition. Compartment structure and CTCFs are indicated for this region beneath the maps. Images show snapshots of polymer simulation with a single Dag1 region colored. Boxed images at the bottom show snapshots of a 0.385-Mb segment of the Dag1 region with A and B monomers (blue and red) made transparent to highlight microcompartments (magenta). f, Quantification of percentage change in loop strength of simulated microcompartments from AT to LG1 as a function of loop size (left) and average microcompartment and CTCF loop strengths (middle) throughout the M-to-G1 transition, the same as in Fig. 3c,d. Right, microcompartment loop strengths scaled by mean PM loop strength for simulations (blue) and corresponding P–P, E–P and E–E loops in the Dag1 region in experiments (gray).
