Figure 2.

Variations of the Two Model Parameters Reproduce Chromatin Organization in Growing, Senescent, and Progeroid Cells

(A) A heatmap showing the distance $\overline{z}$ between the center of mass of the chromosome from the NL across the parameter space $\left({\mathrm{ϵ}}_{\text{HH}},{\mathrm{ϵ}}_{\text{HL}}\right)$. Ten simulations were performed for every 0.2 increment in both ${\mathrm{ϵ}}_{\text{HH}}$ and ${\mathrm{ϵ}}_{\text{HL}}$ directions. Distances are reported in units of the bead size ($\sigma \approx 70$ nm). The pink line separating the adsorbed and desorbed regime was estimated based on the inflection points in $\overline{z}$ when varying ${\mathrm{ϵ}}_{\text{HL}}$ for fixed ${\mathrm{ϵ}}_{\text{HH}}$. $\overline{z}$ also captures the transition between the collapsed and extended phase in the adsorbed regime, as a compact fiber would stay closer to the NL. The cyan line reports the inflection points at which this transition occurs.

(B) A heatmap showing the average local number density $\rho$ of chromatin beads across the parameter space. The cyan line separating the extended and collapsed phases was estimated based on the inflection points in $\rho$. Its location is consistent with that estimated from $\overline{z}$. The interaction strengths for extended and collapsed conformation are also in line with recent studies on chromatin structure in yeast (Socol et al., 2019) and Drosophila (Lesage et al., 2019).

(C) A full-phase diagram of the four observed phases: adsorbed-extended (AE), adsorbed-collapsed (AC), desorbed-extended (DE), and desorbed-collapsed (DC). The boundary lines are those from (A) and (B).

(D) Simulation snapshots of the four phases.

(E) Illustrations of chromatin structures for cells in growing, senescent, and progeroid conditions.

(F) Cross-sectional view of a simulation snapshot corresponding to the DC or senescent phase.

(G) Time-averaged density profiles of HC and EC as a function of distance r from the center of the globule.

(H) Confocal images of chromosomes in senescent cells with DAPI, H3K27me3, and H3K9me3 staining. Scale bars indicate 10 μm.

(I) Enlarged view of an SAHF corresponding to the white square in the combined image in (H).

(J) Corresponding intensity profiles for H3K9me3 and H3K27me3 along the white line in (I).