The Genomic Code for Nucleosome Positioning

Abstract

Eukaryotic genomes encode an additional layer of genetic information that controls the organization of the genomic DNA into arrays of nucleosomes. This information is superimposed (multiplexed) on top of the regulatory and coding information that was previously understood. We have developed an ability to read this nucleosome positioning code and predict the in vivo locations of nucleosomes. In our most recent studies, we developed a "pure" statistical profile of nucleosome DNA sequence preferences by competitive reconstitution of nucleosomes onto genomic DNA in vitro, using a system comprising only purified genomic DNA and purified histones (the protein components of nucleosomes). Using this statistical profile, we find that genome's intrinsically encoded nucleosome positioning information accounts for the overwhelming majority of nucleosome‐occupied versus nucleosome‐depleted regions across the entire genome. Analyses of nucleosome occupancy in different biological conditions reveal that the condition‐specific action of gene regulatory proteins and chromatin remodeling factors lead to specific localized changes in nucleosome occupancy and positioning, leaving much of the chromatin organization unaffected. Our results suggest that genomes utilize the nucleosome positioning code to facilitate specific chromosome functions including to delineate functional versus nonfunctional binding sites for key gene regulatory proteins, and to define the next higher level of chromosome structure itself.