Extra views on structure and dynamics of DNA loops on nucleosomes studied with molecular simulations

Abstract

It has been shown experimentally that the action of the RSC chromatin remodeler leads to the formation of an irregular, partially remodeled nucleosome, termed a remosome. The remosome contains an extra 30-40 base pairs of DNA compared to a canonical nucleosome. Large-scale molecular simulations have provided information on the probable structure of remosomes and have explained why they remain stable in the absence of RSC. Here we explain how these simulations were carried out and what the resulting remosome models imply in terms of the mechanism of action of RSC. We notably show that local kinks within DNA are key in explaining how extra DNA can be in added to nucleosomes without unduly disturbing DNA-histone binding.

Keywords: DNA; DNA kinks; DNA loops; RSC; SWI/SNF; chromatin remodeling; molecular dynamics; nucleosome; remosome.

Figure 1.

Remosome model resulting from a molecular simulation. This snapshot presents the DNA loop generated by a 42 bp insert at the dyad position. The image shows the solvent-excluded surfaces of the histone core (gray) and of the DNA (cyan, partially transparent) as well as the helical axis of the DNA (black). Note the sharp kink within the DNA loop on the left hand side of the image. Molecular graphics were generated with the UCSF Chimera package.

Figure 2.

Remosome model placed within the RSC remodeller. Two views of a nucleosome containing a 42 bp insertions at the dyad (DNA shown in cyan, histone core in gray) manually docked inside the 3D reconstruction of the RSC complex calculated from cryo-EM data. (shown in yellow). A representative snapshot of the remosome model was taken from a 0.5 μs MD simulation converted to a 25 Å-resolution density map to match the RSC data. DNA in the looped nucleosome is shown up to 25 bp from the ends, to account for the possible rearrangements in these zones. Molecular graphics were generated with the UCSF Chimera package.