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Bioinformatics Advance Access originally published online on May 15, 2009
Bioinformatics 2009 25(14):1782-1788; doi:10.1093/bioinformatics/btp323
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Relating periodicity of nucleosome organization and gene regulation

Jun Wan 1, Jimmy Lin 2, Donald J. Zack 1,3,4,5 and Jiang Qian 1,*

1 Wilmer Institute, 2 Celluar & Molecular Medicine Program, 3 Department of Molecular Biology and Genetics, 4 Department of Neuroscience and 5 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

* To whom correspondence should be addressed.


  Abstract

Motivation: The relationship between nucleosome positioning and gene regulation is fundamental yet complex. Previous studies on genomic nucleosome positions have revealed a correlation between nucleosome occupancy on promoters and gene expression levels. Many of these studies focused on individual nucleosomes, especially those proximal to transcription start sites. To study the collective effect of multiple nucleosomes on the gene expression, we developed a mathematical approach based on autocorrelation to relate genomic nucleosome organization to gene regulation.

Results: We found that nucleosome organization in gene promoters can be well described by autocorrelation transformation. Some promoters show obvious periods in their nucleosome organization, while others have no clear periodicity. The genes with periodic nucleosome organization in promoters tend to be lower expressed than the genes without periodic nucleosome organization. These suggest that regular organization of nucleosomes plays a critical role in gene regulation. To quantitatively associate nucleosome organization and gene expression, we predicted gene expression solely based on nucleosome status and found that nucleosome status accounts for ~25% of the observed gene expression variability. Furthermore, we explored the underlying forces that maintain the periodicity in nucleosome organization, namely intrinsic (i.e. DNA sequence) and extrinsic forces (i.e. chromatin remodeling factors). We found that the extrinsic factors play a critical role in maintaining the periodic nucleosome organization.

Contact: jiang.qian{at}jhmi.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: David Rocke

Received on February 21, 2009; revised on April 20, 2009; accepted on May 12, 2009

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