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


CONCLUSIONS
An in silico screening approach is presented, which allows increased sensitivity of PPAR binding site and target gene detection.
Heinäniemi
Merja
M
Department of Biochemistry, University of Kuopio, FIN-70211 Kuopio, Finland.
Uski
J Oskari
JO
Degenhardt
Tatjana
T
Carlberg
Carsten
C
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA / Q000379:methods*
D047492:Peroxisome Proliferator-Activated Receptors