One-base-pair localization of nucleosomes

Nucleosome position plays a key role in eukaryotic gene regulation, and its precise measurement is critical to understanding all DNA-templated events, but insufficient information has been available to infer nucleosome position at single-base-pair (1-bp) resolution. Brogaard et al. therefore developed an in vivo nucleosome-mapping method, based on the direct incorporation of a label into the nucleosome core, that generates hydroxyl radicals that cleave nucleosomal DNA at defined positions. This method allows direct measurement of nucleosome position with unmatched accuracy. Here we present a new algorithm that uses the Brogaard et al. data to achieve 1-bp resolution by using a joint cleavage pattern of radicals on Watson and Crick strands and can localize nucleosomes that are adjacent to each other. This algorithm provides the highest-resolution nucleosome-position maps to date and will allow detailed analysis of chromatin organization and protein-interaction dynamics.