New Insights into Nucleosome Unwrapping

Abstract

Recently, a new approach for direct mapping of nucleosome centers at base-pair resolution was developed [1] and some intriguing results appeared. About 40% of the inter-dyad distances are smaller than 147 base-pairs, which indicates massive nucleosome unwrapping, genome-wide, in vivo. Paired-end reads give, for the first time, precise information about neighboring nucleosomes which come from the same cell. The histogram of the inter-dyad distances presents small oscillations with the period of about 10 base-pairs. These oscillations indicate a step-wise unwrapping of the nucleosomal DNA from the histone.One-dimensional lattice models can reproduce characteristic patterns observed in the distribution of the nucleosomes along the chromosomes [2, 3]. We present a statistical mechanics model [4] for the nucleosome unwrapping, which is able to take into account sequence-dependent binding energies, sequence-independent potential barriers and wells, effective two-body interactions between the nucleosomes, competition between different species (e.g. nucleosomes and transcription factors, RNA polymerase, etc.), cooperative-binding, and other important factors which dictate the nucleosome distribution along the DNA. We solve both the direct and the inverse problems.Using our model, we are able to reproduce the distribution of the inter-dyad distances, which clearly cannot be obtained using the assumption that all histones cover the same length of DNA (i.e. there is no unwrapping).An extended abstract can be found here: http://www.physics.rutgers.edu/∼rchereji/unwrap.pdf