Email updates

Keep up to date with the latest news and content from Genome Biology and BioMed Central.

Open Access Highly Accessed Research

Meta-analysis of primary target genes of peroxisome proliferator-activated receptors

Merja Heinäniemi12, J Oskari Uski1, Tatjana Degenhardt1 and Carsten Carlberg12*

Author Affiliations

1 Department of Biochemistry, University of Kuopio, FIN-70211 Kuopio, Finland

2 Life Sciences Research Unit, University of Luxembourg, L-1511 Luxembourg

For all author emails, please log on.

Genome Biology 2007, 8:R147  doi:10.1186/gb-2007-8-7-r147

Published: 25 July 2007

Abstract

Background

Peroxisome proliferator-activated receptors (PPARs) are known for their critical role in the development of diseases, such as obesity, cardiovascular disease, type 2 diabetes and cancer. Here, an in silico screening method is presented, which incorporates experiment- and informatics-derived evidence, such as DNA-binding data of PPAR subtypes to a panel of PPAR response elements (PPREs), PPRE location relative to the transcription start site (TSS) and PPRE conservation across multiple species, for more reliable prediction of PPREs.

Results

In vitro binding and in vivo functionality evidence agrees with in silico predictions, validating the approach. The experimental analysis of 30 putative PPREs in eight validated PPAR target genes indicates that each gene contains at least one functional, strong PPRE that occurs without positional bias relative to the TSS. An extended analysis of the cross-species conservation of PPREs reveals limited conservation of PPRE patterns, although PPAR target genes typically contain strong or multiple medium strength PPREs. Human chromosome 19 was screened using this method, with validation of six novel PPAR target genes.

Conclusion

An in silico screening approach is presented, which allows increased sensitivity of PPAR binding site and target gene detection.