Screening for PPAR Responsive Regulatory Modules in Cancer

Peroxisome proliferator-activated receptors (PPARs) have via their large set of target genes a critical impact on numerous diseases including cancer. Cancer development involves numerous regulatory cascades that drive the progression of the malignancy of the cells. On a genomic level, these pathways converge on regulatory modules, some of which contain colocalizing PPAR binding sites (PPREs). We developed an in silico screening method that incorporates experiment- and informatics-derived evidence for a more reliable prediction of PPREs and PPAR target genes. This method is based on DNA-binding data of PPAR subtypes to a panel of DR1-type PPREs and tracking the enrichment of binding sites from multiple species. The ability of PPARγ to induce cellular differentiation and the existence of FDA-approved PPARγ agonists encourage the exploration of possibilities to activate or inactivate PPRE containing modules to arrest cancer progression. Recent advances in genomic techniques combined with computational analysis of binding modules are discussed in the review with the example of our recent screen for PPREs on human chromosome 19.