Our chromatin mesoscale model and modeling of Myc:Max binding to chromatin and the Eed gene.

A) Coarse grained chromatin elements (nucleosome core, linker DNA, histone tails, and LH) form chromatin fibers at the kb level. B) Crystal structure of Myc:Max forming a heterotetramer that binds to sequence-distant DNA regions. C) Schematic representation of Myc:Max heterodimers and heterotetramers. D) Illustration of our implicit modeling of Myc:Max binding to chromatin fibers: distance constraints following Hooke’s spring law are enforced when two linker DNAs with Myc:Max bound are in close spatial proximity (20 nm) and at at least 30 linker DNAs apart. E) Design of the Eed gene loci using Mnase-seq data to position NFRs (orange track) and Chip-seq data to position LHs (blue track) and Myc:Max binding regions (green track).

TF binding location drives formation of microdomains.

50-nucleosome chromatin fibers with: A) 44 bp linkers, B) 62 bp linkers, C) 26 bp linkers, and D) Non uniform linkers simulated with 4 different TF topologies. At the top, for the 44 bp system, we show an ideal zigzag fiber coloring in red the DNA with TF binding regions. Arcs show the possible binding geometries. The binding positions and geometries that define each topology are the same in all systems. For each system, we show the cumulative contact map calculated from 10 independent trajectories and a representative fiber structure also showing in red the TF binding regions. Additional representative structures are shown in Figures S2, S3, S4, and S5.

Microdomains emerge only from ensemble-based contact maps.

The 10 single-trajectory contact maps for the 62 bp system Topology 1 (5 TF binding regions) at left reveal various microdomains. The large ensemble-based contact map at right obtained by summing the 10 individual contact maps reveals all possible microdomains contacts.

TF saturation curves are affected by histone acetylation and LH.

The graphs A–C show packing ratios and sedimentation coefficients as a function of TF concentration for the 26 bp, 44 bp, 62 bp, and Life-Like fibers in different conditions: A) systems without LH and acetylation; B) systems with two acetylation islands; and C) systems with LH density ρ = 1. At top left, we show the fiber axis (red trace) and position of nucleosomes (blue dots) for a 70 bp chromatin fiber to illustrate the increase of packing ratio (number of nucleosomes per 11 nm of fiber length) upon TF binding. At top right, we show a 70 bp linker chromatin fiber to illustrate the decrease of chromatin global size upon TF binding. Results including uniform systems with 35, 53, 79, and 80 bp are shown in Figure S6.

TF binding affects chromatin architecture.

Chromatin uniform fibers of 44, 62, and 26 bp linkers, as well as non uniform Life-Like fibers at increasing TF concentration. WT shows structures of the wildtype systems (no acetylation and no LH). +Ac shows structures of the acetylated systems with acetylated tails drawn in red and wildtype tails in blue. +LH shows structures of systems with an LH density of 1 LH/nucleosome, with LHs drawn in cyan.

TF binding repress the Eed gene loci.

A) Ensemble based nucleosome contact maps obtained from 20 independent trajectories of the Eed gene in absence and presence of TF binding. B) Nucleosome contact maps obtained from a single trajectory of the Eed gene in absence and presence of TF binding. C) Representative chromatin fibers of the Eed gene in absence and presence of TF binding. In magenta are shown the TF binding regions. LHs are shown in cyan.

Compaction parameters: Sedimentation coefficient and radius of gyration for the entire Eed system, and area and volume for the promoter region of Eed.

Activation of the Eed gene loci depends on LH density.

A) Ensemble based nucleosome contact maps obtained from 20 independent trajectories of the Eed gene with an LH density of 0.8 LH/nucleosome in absence and presence of TF binding. B) Representative chromatin fibers of the Eed gene in absence and presence of TF binding showing that the two TF binding regions remain apart upon TF binding. In magenta are shown the TF binding regions. LHs are shown in cyan.