Dynamical DNA accessibility induced by chromatin remodeling and protein binding

Chromatin remodeling factors are enzymes being able to alter locally chromatin structure at the nucleosomal level and they actively participate in the regulation of gene expression. Using simple rules for individual nucleosome motion induced by a remodeling factor, we designed simulations of the remodeling of oligomeric chromatin, in order to address quantitatively collective effects in DNA accessibility upon nucleosome mobilization. Our results suggest that accessibility profiles are inhomogeneous thanks to borders effects like protein binding. Remarkably, we show that the accessibility lifetime of DNA sequence is roughly doubled in the vicinity of borders as compared to its value in bulk regions far from the borders. These results are quantitatively interpreted as resulting from the confined diffusion of a large nucleosome depleted region.

Figure 1

Comparison of nucleosomal profiles after thermal and RSC mobilization. (a) Average nucleosomal DNA, in the common starting configuration (left), after 2000 steps of thermal (center) and RSC (right) mobilization. Snapshots of nucleosomal DNA at different times for thermal (b) and for RSC (c) mobilization. Parameters for this figure are $N=20,L_k=50\text{bp},2000$ runs. Cartoons have illustrative purposes for typical stationary configurations for thermal and RSC mobilization, but not at proper scale.

Figure 2

Dependence of average nucleosomal profile in $N$ and $L_k$ for thermal (left panel) and RSC (right panel) mobilization. The four curves on each panel are associated with parameters: $N=20$ and $L_k=50$ bp (dark thick line), $N=20$ and $L_k=20$ bp (light thick line), $N=40$ and $L_k=50$ bp (bottom thin line), $N=40$ and $L_k=20$ bp (upper thin line). Other common parameters: $2000$ steps, $2000$ runs.

Figure 3

DNA accessibility lifetime upon RSC mobilization at discrete sites hidden by nucleosomes in the starting configuration. (a) Average accessibility lifetime for $N=6$ (lower blue line with circles), $N=20$ (middle green line with circles), $N=40$ (upper red line with circles). The dotted lines correspond to the average accessibility lifetime for thermal mobilization for $N=20$ (light cyan) and $N=40$ (dark purple). Other common parameters: $L_k=50\text{bp},2000$ steps, $2000$ runs. (b) Accessibility lifetime distribution in logarithmic color scale for $N=20$. The green curve corresponds to the average accessibility lifetime. (c) Cartoons for $N=6$ showing only one entry or one exit (yellow star) for accessibility event (top, red light stick), and two entries or two exits (down, dark blue stick). The configurations allowing accessibility of sites are highlighted by the change of color of the sticks (light yellow sticks).

Figure 4

Comparison of nucleosomal DNA and average accessibility lifetime after protein binding at different locations $L_{\text{prot}}$. (a) $L_{\text{prot}}=L_{\text{tot}}/2$, (b) $L_{\text{prot}}=L_{\text{tot}}/3$, (c) $L_{\text{prot}}=L_{\text{tot}}/4$, (d) $L_{\text{prot}}=L_{\text{tot}}/5$. For each panel, the top (blue) curve is the nucleosomal DNA, while the lower (green) curve is the average accessibility lifetime. Thin (red) dotted lines represent the average accessibility lifetime before binding. Other common parameters: $N=40,L_k=50\text{bp},4000$ steps, 500 runs.