Physiol. Genomics AJP: Lung Cellular and Molecular Physiology
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Physiol. Genomics 31: 374-384, 2007. First published September 11, 2007; doi:10.1152/physiolgenomics.00085.2006
1094-8341/07 $8.00
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Received 10 May 2006; accepted in final form 4 September 2007.
Physiological Genomics 31:374-384 (2007)
1094-8341/06 $8.00 © 2007 American Physiological Society

Call For Papers: Comparative Genomics

Identifying cis-regulatory elements by statistical analysis and phylogenetic footprinting and analyzing their coexistence and related gene ontology

Wei Shi1, Wanlei Zhou2 and Dakang Xu3

1 Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne; Australia
2 School of Engineering and Information Technology, Deakin University, Melbourne; Australia
3 Centre for Cancer Research, Monash Institute of Medical Research, Monash University, Melbourne, Australia

Discovery of cis-regulatory elements in gene promoters is a highly challenging research issue in computational molecular biology. This paper presents a novel approach to searching putative cis-regulatory elements in human promoters by first finding 8-mer sequences of high statistical significance from gene promoters of humans, mice, and Drosophila melanogaster, respectively, and then identifying the most conserved ones across the three species (phylogenetic footprinting). In this study, a conservation analysis on both closely related species (humans and mice) and distantly related species (humans/mice and Drosophila) is conducted not only to examine more candidates but also to improve the prediction accuracy. We have found 124 putative cis-regulatory elements and grouped these into 20 clusters. The investigation on the coexistence of these clusters in human gene promoters reveals that SP1, EGR, and NRF-1 are the dominant clusters appearing in the combinatorial combination of up to five clusters. Gene Ontology (GO) analysis also shows that many GO categories of transcription factors binding to these cis-regulatory elements match the GO categories of genes whose promoters contain these elements. Compared with previous research, the contribution of this study lies not only in the finding of new cis-regulatory elements, but also in its pioneering exploration on the coexistence of discovered elements and the GO relationship between transcription factors and regulated genes. This exploration verifies the putative cis-regulatory elements that have been found from this study and also gives new insight on the regulation mechanisms of gene expression.

transcription factor






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