Computational modeling of chromatin domain network via active RNAPII. Brownian dynamics of four chains of chromatin domains (green spheres) connected by springs (invisible) and four hubs, clusters of P-TEFb (pink spheres), were simulated in a box with the side length of 1.5 µm with the periodic boundary condition. Chromatin chains bind Nglue RNAPII-Ser5P (red spheres), and attractive interactions were assumed between RNAPII-Ser5P–bound chromatin and P-TEFb clusters. (A) Left: A snapshot of the Brownian dynamics with no glues (without RNAPII-Ser5P). Coarse-grained 100-kb chromatin domains (green spheres) connected by invisible springs and the hubs of P-TEFb clusters (faint pink spheres) are shown. See also Video 5. Right: A snapshot of the Brownian dynamics with 64 glues of RNAPII-Ser5P (red spheres). In each of the four chromatin chains, 80 beads are connected by springs with each bead representing a 100-kb chromatin domain. For better visualization of their spatial distributions, green, red, and pink spheres are drawn with the radius of 90, 60, and 180 nm, respectively, although the SDs of their density distributions assumed in the model are ≈ 70, 70, and 210 nm. See also Video 6. (B) MSD plots calculated with various glue numbers bound on chromatins: Nglue = 0 (black), 24 (dark blue), 40 (light blue), and 64 (pink). MSD plots were averaged over all the chromatin domains in the system and over 10 systems having different positions of RNAPII-Ser5P–binding sites. The plots were fitted as a subdiffusive curve: MSD = 0.054t0.64 without glues; MSD = 0.031t0.50 with Nglue = 64. The bars represent standard errors. ***, P < 0.0001 (P = 1.0 × 10−8) by Student’s t test. (C) The MSD (0.5 s) distribution plots of total beads with (pink) and without RNAPII-Ser5P glues (black). Note that there are a slow and fast bead fraction with RNAPII-Ser5P glues. The slow fraction (arrow) lowers the ensemble average of total beads dynamics in the system. Images in A were drawn with the software OVITO (Stukowski, 2010).
