The spring-loaded genome: Nucleosome redistributions are widespread, transient, and DNA-directed
- Brittany S. Sexton1,
- Denis Avey1,
- Brooke R. Druliner1,
- Justin A. Fincher1,
- Daniel L. Vera1,
- Daniel J. Grau2,
- Mark L. Borowsky2,5,
- Shobhit Gupta3,6,
- Senthil B. Girimurugan4,
- Eric Chicken4,
- Jinfeng Zhang4,
- William S. Noble3,
- Fanxiu Zhu1,
- Robert E. Kingston2 and
- Jonathan H. Dennis1,7
- 1Department of Biological Science, The Florida State University, Tallahassee, Florida 32306-4295, USA;
- 2Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA;
- 3Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
- 4Department of Statistics, The Florida State University, Tallahassee, Florida 32306-4295, USA
Abstract
Nucleosome occupancy plays a key role in regulating access to eukaryotic genomes. Although various chromatin regulatory complexes are known to regulate nucleosome occupancy, the role of DNA sequence in this regulation remains unclear, particularly in mammals. To address this problem, we measured nucleosome distribution at high temporal resolution in human cells at hundreds of genes during the reactivation of Kaposi's sarcoma–associated herpesvirus (KSHV). We show that nucleosome redistribution peaks at 24 h post-KSHV reactivation and that the nucleosomal redistributions are widespread and transient. To clarify the role of DNA sequence in these nucleosomal redistributions, we compared the genes with altered nucleosome distribution to a sequence-based computer model and in vitro–assembled nucleosomes. We demonstrate that both the predicted model and the assembled nucleosome distributions are concordant with the majority of nucleosome redistributions at 24 h post-KSHV reactivation. We suggest a model in which loci are held in an unfavorable chromatin architecture and “spring” to a transient intermediate state directed by DNA sequence information. We propose that DNA sequence plays a more considerable role in the regulation of nucleosome positions than was previously appreciated. The surprising findings that nucleosome redistributions are widespread, transient, and DNA-directed shift the current perspective regarding regulation of nucleosome distribution in humans.
Footnotes
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↵7 Corresponding author
E-mail dennis{at}bio.fsu.edu
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.160150.113.
- Received July 1, 2013.
- Accepted November 27, 2013.
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