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J. Lipid Res.
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A more recent version of this article appeared on July 1, 2006

Papers In Press, published online ahead of print April 3, 2006
J. Lipid Res., doi:10.1194/jlr.M500504-JLR200
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Submitted on November 17, 2005
Revised on March 30, 2006
Accepted on April 3, 2006

Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics

Danielle G. Lemay and Daniel H. Hwang

USDA-ARS Western Human Nutrition Research Center and Department of Nutrition, University of California-Davis, Davis, CA 95616

Corresponding Author: dhwang{at}whnrc.usda.gov

Peroxisome proliferator activated receptor (PPAR) agonists are currently used therapeutically in humans even though many of their direct gene targets may be unknown. Since PPARs can directly regulate gene expression through peroxisome proliferator response elements (PPREs), we pursued the computational prediction of PPREs on a genome-wide scale. Contrary to current hypotheses, PPREs are not isotype-specific nor do flanking nucleotides confer additional information. However, a position weight matrix (PWM)-based search for PPREs within upstream conserved elements yielded sufficient selectivity for a genome-wide search. Additionally, a novel motif occuring with greater prevalence than PPREs is revealed. Microarray and gene ontology analyses further validate our search technique and provide new functional clusters of genes that were not previously known to be directly regulated by PPARs (e.g. chromatin remodeling, DNA damage response, Wnt and MAPK signaling). This first genome-wide library of high-confidence predicted PPAR target genes will be a valuable resource to PPAR biologists.


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