Nucleosome fragility reveals novel functional states of chromatin and poises genes for activation
- 1Division of Biostatistics, Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA;
- 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
- 3Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA
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↵4 These authors contributed equally to this work.
Abstract
The structural complexity of nucleosomes underlies their functional versatility. Here we report a new type of complexity—nucleosome fragility, manifested as high sensitivity to micrococcal nuclease, in contrast to the common presumption that nucleosomes are similar in resistance to MNase digestion. Using differential MNase digestion of chromatin and high-throughput sequencing, we have identified a special group of nucleosomes termed “fragile nucleosomes” throughout the yeast genome, nearly 1000 of which were at previously determined “nucleosome-free” loci. Nucleosome fragility is broadly implicated in multiple chromatin processes, including transcription, translocation, and replication, in correspondence to specific physiological states of cells. In the environmental-stress-response genes, the presence of fragile nucleosomes prior to the occurrence of environmental changes suggests that nucleosome fragility poises genes for swift up-regulation in response to the environmental changes. We propose that nucleosome fragility underscores distinct functional statuses of the chromatin and provides a new dimension for portraying the landscape of genome organization.
Footnotes
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↵5 Corresponding authors.
E-mail ruichen{at}bcm.edu.
E-mail WL1{at}bcm.edu.
E-mail xhe{at}bcm.edu.
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[Supplemental material is available for this article. The data from this study have been submitted to the Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo) under accession no. GSE26412.]
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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.117101.110.
- Received May 22, 2010.
- Accepted February 16, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
