Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Research article

Prediction and analysis of nucleosome exclusion regions in the human genome

Ahmed Radwan1, Akmal Younis1, Peter Luykx2 and Sawsan Khuri3*

Author Affiliations

1 Department of Electrical and Computer Engineering, University of Miami College of Engineering, Coral Gables, FL 33124, USA

2 Department of Biology, University of Miami, Coral Gables, FL 33124, USA

3 Center for Computational Science, and the Dr. John T. Macdonald Foundation Department of Human Genetics and Genomic Medicine, University of Miami Miller School of Medicine, Miami, FL 33136 USA

For all author emails, please log on.

BMC Genomics 2008, 9:186  doi:10.1186/1471-2164-9-186

Published: 22 April 2008

Abstract

Background

Nucleosomes are the basic structural units of eukaryotic chromatin, and they play a significant role in regulating gene expression. Specific DNA sequence patterns are known, from empirical and theoretical studies, to influence DNA bending and flexibility, and have been shown to exclude nucleosomes. A whole genome localization of these patterns, and their analysis, can add important insights on the gene regulation mechanisms that depend upon the structure of chromatin in and around a gene.

Results

A whole genome annotation for nucleosome exclusion regions (NXRegions) was carried out on the human genome. Nucleosome exclusion scores (NXScores) were calculated individually for each nucleotide, giving a measure of how likely a specific nucleotide and its immediate neighborhood would impair DNA bending and, consequently, exclude nucleosomes. The resulting annotations were correlated with 19055 gene expression profiles. We developed a new method based on Grubbs' outliers test for ranking genes based on their tissue specificity, and correlated this ranking with NXScores. The results show a strong correlation between tissue specificity of a gene and the propensity of its promoter to exclude nucleosomes (the promoter region was taken as -1500 to +500 bp from the RefSeq-annotated transcription start site). In addition, NXScores correlated well with gene density, gene expression levels, and DNaseI hypersensitive sites.

Conclusion

We present, for the first time, a whole genome prediction of nucleosome exclusion regions for the human genome (the data are available for download from Additional Materials). Nucleosome exclusion patterns are correlated with various factors that regulate gene expression, which emphasizes the need to include chromatin structural parameters in experimental analysis of gene expression.