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Nucleic Acids Research Advance Access published online on September 18, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp743
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Computational Biology

Impact of DNA-binding position variants on yeast gene expression

Krishna B. S. Swamy1,2,3, Chung-Yi Cho1,4, Sufeng Chiang1, Zing Tsung-Yeh Tsai1,2,3 and Huai-Kuang Tsai1,2,4,*

1Institute of Information Science, 2Bioinformatics Program, Taiwan International Graduate Program, 3Institute of Biomedical Informatics, National Yang-Ming University and 4Research Center for Information Technology Innovation, Academia Sinica, Taipei 115, Taiwan

*To whom correspondence should be addressed. Tel: +886 2 278 83799; Email: hktsai{at}iis.sinica.edu.tw

Received May 27, 2009. Revised August 4, 2009. Accepted August 24, 2009.

Transcription factors (TFs) regulate gene expression by binding to specific binding sites (TFBSs) in gene promoters. TFBS motifs may contain one or more variable positions. Although the prevailing assumption is that nucleotide variants at such positions are functionally equivalent, there is increasing evidence that such variants play a role in regulation of gene expression. In this article, we propose a method for studying the relationship between the expression of target genes and nucleotide variants in TFBS motifs at a genome-wide scale in Saccharomyces cerevisiae, especially the combinatorial effects of variants at two positions. Our analysis shows that nucleotide variations in more than one-third of variable positions and in 20% of dependent position pairs are highly correlated to gene expression. We define such positions as ‘functional’. However, some positions are only functional as dependent pairs, but not individually. In addition, a significant proportion of the functional positions have been well conserved across all yeast-related species studied. We also find that some positions require the presence of co-occurring TFs, while others maintain their functionality in the absence of a co-occurring TF. Our analysis supports the importance of nucleotide variants at variable positions of TFBSs in gene regulation.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


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