Nucleic Acids Research Advance Access published online on November 6, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn866
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Computational Biology |
High-throughput chromatin information enables accurate tissue-specific prediction of transcription factor binding sites
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
*To whom correspondence should be addressed. Tel: +61 7 3346 2614; Fax: +61 7 3346 2103; Email: t.bailey{at}imb.uq.edu.au
Received June 9, 2008. Revised October 16, 2008. Accepted October 17, 2008.
In silico prediction of transcription factor binding sites (TFBSs) is central to the task of gene regulatory network elucidation. Genomic DNA sequence information provides a basis for these predictions, due to the sequence specificity of TF-binding events. However, DNA sequence alone is an impoverished source of information for the task of TFBS prediction in eukaryotes, as additional factors, such as chromatin structure regulate binding events. We show that incorporating high-throughput chromatin modification estimates can greatly improve the accuracy of in silico prediction of in vivo binding for a wide range of TFs in human and mouse. This improvement is superior to the improvement gained by equivalent use of either transcription start site proximity or phylogenetic conservation information. Importantly, predictions made with the use of chromatin structure information are tissue specific. This result supports the biological hypothesis that chromatin modulates TF binding to produce tissue-specific binding profiles in higher eukaryotes, and suggests that the use of chromatin modification information can lead to accurate tissue-specific transcriptional regulatory network elucidation.