Sexton, BS, Avey, D, Druliner, BR, Fincher, JA, Vera, DL, Grau, DJ, Borowsky, ML, Gupta, S, Girimurugan, SB, Chicken, E, Zhang, J, Noble, WS, Zhu, F, Kingston, RE and Dennis, JH (2014) The spring-loaded genome: Nucleosome redistributions are widespread, transient, and DNA-directed. Genome Research. pp. 251-259.

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. 2014 Hansen et al

Item Type:	Article
Additional Information:	NIBR author: Borowsky, M institute: NIBR- address only contributor address: (Sexton, Avey, Druliner, Fincher, Vera, Zhu, Dennis) Department of Biological Science, Florida State University, Tallahassee, FL 32306-4295, United States (Grau, Borowsky, Kingston) Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States (Gupta, Noble) Department of Genome Sciences, University of Washington, Seattle, WA 98195, United States (Girimurugan, Chicken, Zhang) Department of Statistics, Florida State University, Tallahassee, FL 32306-4295, United States (Borowsky) Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, MA 02139, United States (Gupta) UBS Investment Bank, Zurich 8050, Switzerland
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22653