Studies of nucleosome-decorated DNA structures and deformations using a new analytical model

The two meters of DNA found in almost every human cell must be folded by many orders of magnitude to fit in the nucleus. The first step in this compaction involves the coiling of ~150 base pairs of DNA around a core of eight positively charged histone proteins. Understanding the biological processing of DNA requires knowledge of how the nucleosomes are arranged in space. We introduce a new analytical treatment of nucleosome-decorated DNA which is made up of three essential parts: nucleosomal DNA; protein-free stretches of DNA; and the intervening connectors. Every connector provides a physically smooth DNA pathway between a protein-bound and/or a protein-free segment. We have used this approach to study the energetically preferred configurations of torsionally relaxed, 360-base pair DNA rings with two evenly-spaced nucleosomes as well as rings of the same size with a single nucleosome subject to deformation in structure and/or variation in DNA wrapping. We have identified conditions where the closed DNA chain switches from one global configuration state to another. We are also using this model to study more complicated structures, such as the Simian virus 40 minichromosome, an assembly of ~20 nucleosomes on ~5200 base pairs of DNA supercoiling.