Mesoscale simulations of two nucleosome-repeat length oligonucleosomes

Abstract

The compaction of chromatin, accessed through coarse-grained modeling and simulation, reveals different folding patterns as a function of the nucleosome repeat length (NRL), the presence of the linker histone, and the ionic strength. Our results indicate that the linker histone has negligible influence on short NRL fibers, whereas for longer NRL fibers it works like, and in tandem with, concentrated positive counterions to condense the chromatin fiber. Longer NRL fibers also exhibit structural heterogeneity, with solenoid-like conformations viable in addition to irregular zigzags. These features of chromatin and associated internucleosomal patterns presented here help interpret structural dependencies of the chromatin fiber on internal and external factors. In particular, we suggest that longer-NRL are more advantageous for packing and achieving various levels of fiber compaction throughout the cell cycle.

Figure 1. The mesoscale model and basic chromatin fiber structures

a) The mesoscale model of the basic chromatin building block. b) Beads-on-a-string fiber structure at low monovalent salt (0.01 M). c) An ideal zigzag configuration of the chromatin fiber with the nucleosome contact pattern. d) An ideal solenoid configuration of the chromatin fiber with the nucleosome contact pattern.

Figure 2. Fiber structures for two NRLs under different conditions for 24-core arrays

For each case, the dominant zigzag conformation is shown and, for two cases where a solenoid conformation also exist, both the zigzag and solenoid models are shown. The turquoise beads indicate linker histones. Various nucleosome contacts are illustrated to help interpret the profiles in Figure 3.

Figure 2. Fiber structures for two NRLs under different conditions for 24-core arrays

For each case, the dominant zigzag conformation is shown and, for two cases where a solenoid conformation also exist, both the zigzag and solenoid models are shown. The turquoise beads indicate linker histones. Various nucleosome contacts are illustrated to help interpret the profiles in Figure 3.

Figure 3. Contact patterns and bending angles under different experimental conditions

a, b) The contact patterns for the 173 (Fig. 3a) and 209 bp (Fig. 3b) NRL fibers at 4 conditions as shown in the inset. c) The bending angle distribution for the 209 bp NRL fibers at 4 conditions as shown in the inset. See Fig. 2 for nucleosome contact illustrations.

Figure 4. Tail distributions for a typical fiber configuration within a nucleosome and within the fiber with linker histone at 0.15 M salt

The dots represent tail bead positions according to the color code shown. The positions of the three linker histone beads are shown as white circles.

Figure 5. Linker DNA positional distribution for a typical fiber configuration for various conditions projected on the nucleosome and dyad plane

The red dots represent linker DNA bead positions. The mean trajectories of the DNA linkers are shown as blue lines. The positions of the three linker histone beads are shown as black circles.