Genome-Wide Kinetics of Nucleosome Turnover Determined by Metabolic Labeling of Histones

Everything Changes Nucleosomes package DNA, and their assembly and disassembly regulate access to the genome. The ability to follow these changes is limited to steady-state methods in higher eukaryotes, although direct kinetic analyses are available in yeast. To address this deficiency, Deal et al. (p. 1161) developed a general method for following the genome-wide dynamics of nucleosome assembly and disassembly. High levels of nucleosome turnover were observed across gene bodies and at the sites of epigenetic regulatory elements in fruit fly tissue culture cells. Nucleosomes were replaced multiple times during each 20-hour cell cycle, suggesting that histone modifications themselves are unlikely to transmit epigenetic information. Furthermore, analysis of replication origins indicates that they are determined by chromatin dynamics and not by sequence features. Differences between active and silent chromatin states are critical for maintaining the epigenome. Nucleosome disruption and replacement are crucial activities that maintain epigenomes, but these highly dynamic processes have been difficult to study. Here, we describe a direct method for measuring nucleosome turnover dynamics genome-wide. We found that nucleosome turnover is most rapid over active gene bodies, epigenetic regulatory elements, and replication origins in Drosophila cells. Nucleosomes turn over faster at sites for trithorax-group than polycomb-group protein binding, suggesting that nucleosome turnover differences underlie their opposing activities and challenging models for epigenetic inheritance that rely on stability of histone marks. Our results establish a general strategy for studying nucleosome dynamics and uncover nucleosome turnover differences across the genome that are likely to have functional importance for epigenome maintenance, gene regulation, and control of DNA replication.