All of the processes necessary for the survival of a eukaryotic cell hinge on the cell's ability to store and read the genetic information encoded in its DNA. The daunting task of packaging the meter-long genome into a micron-sized nucleus is complicated by the necessity of maintaining the accessibility of the DNA to the cell's enzymatic machinery. The fundamental unit of packaged DNA, the nucleosome core particle, contains 146 base pairs of DNA wrapped 1.7 times around a cationic protein complex called the histone octamer. A string of nucleosomes is organized into higher-order structures at several hierarchical levels to form chromatin, a remarkable complex that is compact yet maintains accessibility for gene expression. The interactions between DNA and histones constitute the initial barrier to protein accessibility to chromosomal DNA, thus a quantitative picture of DNA-histone interactions is critical to understand the biological function of chromatin.

We develop a statistical-mechanics model of a nucleosome as a wormlike chain bound to a spool, incorporating fluctuations in the number of bases bound, the spool orientation, and the conformations of the unbound polymer segments. This model is directly compared to single-molecule experiments conducted in Carlos Bustamante's lab; we find good agreement between our theory and the experimental data. We then proceed to consider the role of structural fluctuations in the accessibility of the packaged DNA to regulatory proteins. Nucleosome translocation and transient unwinding are considered as molecular mechanisms for protein accessibility. We discuss the impact of structural fluctuations within the nucleosome core particle on gene regulation.