Additional file 1 of Strong interactions between highly dynamic lamina-associated domains and the nuclear envelope stabilize the 3D architecture of Drosophila interphase chromatin
Creators: name: Tolokh, Igor S.
name: Kinney, Nicholas Allen
name: Sharakhov, Igor V.
name: Onufriev, Alexey V.
Publisher: name: figshare
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Biological Sciences not elsewhere classified
subject: Developmental Biology
subject: Cancer

description: Additional file 1: Figure S1. The number of TADs and LAD containing TADs (L-TADs) in each of the four epigenetic classes of TADs (Active, Null, PcG and HP1) are shown: the numbers of TADs – as solid color bars, the numbers of L-TADs – as bars with diagonal stripes. Figure S2. Determining the interaction strength between the special pairs of TADs. Shown is the logarithm of the ordered (index n) degree of enrichment for the contact probabilities of 268 specific pairs of remote chromatin loci [6] and approximating fit (Eq. S5) used to determine the attractive interaction LJ well depth for the interactions between the beads int hat specific pairs. Figure S3. Time dependence of mean squared displacement (MSD) of bead averaged over 9 beads and 18 trajectories of the model nuclei with different topologies and size, simulated with 3 different values of the friction parameter γ. The simulation data points (symbols with error bars) are fitted with Eq. S7 (dashed lines)– the equation corresponds to theexperimentally observed time dependence of MSD for a chromosomal loci [14]. The fit is used to estimate the simulation time scaling factor λ, which determines the mapping between the simulation time and biological time of a nucleus. Error bars in each curve are RMSD of 9-bead-average values in 18 trajectories. Figure S4. Cumulative normalized distributions of L-TADs (LADcontaining TADs) at different levels of attractive interaction with the nuclear envelope (NE) varying from 0.1 kT to 5 kT. The vertical dashed line at R=1.91 μm marks the center of the bead layer nearest to the NE. Experimental data [15] show that about 25% (horizontal dashed line at 0.75 mark) of LADs are on average located at the NE. Figure S5. Details of the temporal evolution of the WT model derived TAD-TAD contact probability (HiC) maps. The Hi-C maps are averaged over 5 min time intervals and over the ensemble of 18 system trajectories (see "Methods"). The top left panel is t=0 min Hi-C map, followed (from left to right) by the difference (from t=0 min) maps at 30 min, 3 h and 11 h. Figure S6. The effect of complete removal of the NE: chromatin de-compacts. Within 1 min, chromosome 4 dissociates and drifts away from the rest three de-condensed chromosomes. Figure S7. Top panel: Chromatin density distributions in the model nuclei at different levels of LAD-NE attractive interaction (from 0.1 to 5 kT). Bottom panel: Chromatin density distributions in the model nuclei at different levels of attractive interaction between Null TADs. Figure S8. Difference Hi-C map between Lamin mutant model Hi-C map (Fig.5, main text) and the corresponding WT model Hi-C map (Fig. 3, main text, bottom panel). Note that the intensity scale is 10 times smaller here than that of the original Hi-C map, pointing to relatively small differences in TAD-TAD contact probabilities. Most TAD-TAD contacts, including inter-chromosome contacts, are slightly enhanced (red areas) in the Lamin mutant compared to the WT nuclei. Small areas where the contact frequency decreases (blue spots) in the Lamin mutant are limited to close to diagonal intra-arm contacts. Figure S9. Increasing the cross-type TAD-TAD interactions from 0.5 kT (model selected) to 1.0 kT results in increased TAD-TAD contact probabilities, both in WT and Lamin mutant model nuclei. The Hi-C map differences between modified and selected model nuclei are shown. (Top panel:) for the WT model nuclei. (Bottom panel:) for the Lamin mutant model nuclei. Figure S10. The mobility of five select L-TADs over about two minutes time interval of the interphase, starting at t = 0. Shown are four snapshots from the supplementary movie that represents 20 minutes of time-evolution of model fruit fly nucleus. Each L-TAD is selected from a different chromosome. The L-TADs represented by orange, green, grey, red and blue are from Chr 2L, 2R, 3L, 3R and Chr X, respectively. All other beads, including the large heterochromatic beads, are shown as transparent grey spheres. The upper panel snapshots, from left to right, correspond t = 0.04(s) and t = 0.28(s), respectively. The lower panel snapshots, from left to right, correspond to t = 35.5(s) and t = 104(s), respectively. The coordinate frame vectors are shown in the left corner of each panel. Apparent variation in each L-TAD sphere size conveys the depth perception: spheres closer to the viewer are larger. Image Credit: Samira Mali. Rendering by VMD [17]. Visualization of motion of these L-TADs, from 3 different viewing angles, is available as supplementary movies (Additional files 2, 3 and 4). Figure S11. The sums of contact probabilities of Null TADs (B-type TADs) with Active TADs (A-type TADs) only, calculated from the model Hi-C maps for the WT nuclei (red circles) and Lamin mutant nuclei (green circles), for each Null TAD. The average relative increase of the contact probabilities for Lamin mutant Null TADs is 22%. Figure S12. Predicted cumulative frequencies of radial positions of three cytological regions for which the corresponding experimental data is available. Top panel: Cumulative frequencies of radial positions of the Null L-TAD #15 (cytological region 22A in Ref. [16]) in the WT and Lamin mutant nucleus models. Middle panel: Cumulative frequencies of radial positions of the Null L-TAD #120 (cytological region 36C in Ref. [16]) in the WT and Lamin mutant model nuclei. Bottom panel: Cumulative frequencies of radial positions of the PcG L-TAD #435 (cytological region60D in Ref. [16]) in the WT and Lamin mutant nucleus models.