DNA Loop Formation in Nucleosomes

Abstract

Many key processes in the cell nucleus, such as replication, transcription or DNA-repair, require the physical accessibility of specific DNA sequences. In eukaryotes, DNA is wrapped in 1.67 left-handed superhelical turns around a histone protein core to form the nucleosome. Although the function of histones in eukaryotes remains elusive, it is possible that histone mobility on DNA is responsible for ‘opening up’ DNA surfaces at different periods of chromatin organization. One of the mechanisms of nucleosome repositioning on DNA involve formation of local defects in the form of a loop and diffusion of it over the stretch of DNA attached to the histone. DNA loop formation has so far been discussed in the context of the worm like chain (WLC) model [1]. However, atomic force microscopy experiments [2] suggest that large angle bending energetics of DNA does not follow a WLC. Here we describe the energetics of loop formation on nucleosomes using a model which offers softer bending potential for large deflections, namely the sub-elastic chain (SEC), and compare with WLC. Results show that SEC favors small loop (∼ 10 bp) formation, WLC favors large loop formation. Different energetics of loop formation also leads to different nucleosome repositioning behaviors for WLC and SEC. Nucleosomes, initially positioned in the middle of a DNA segment, jumps to the extremities for WLC and to the nearest neighboring positions for SEC.1. Kulic I. M., Schiessel H. 2003. Nucleosome repositioning via loop formation. Biophys J., 84(5):3197-211.2. Wiggins et. al. 2006. High flexibility of DNA on short length scales probed by atomic force microscopy. Nature Nanotechnology.1.137.