Negative regulation of gene expression by PPARs. Different mechanisms of transrepression through interference of activated PPARs with activation of transcription factors have been described. (1) Activated PPAR-RXR complexes may sequester essential coactivators shared with other transcription factors. (2) Physical association of PPARs with specific transcription factors results in reduced binding to their cognate response elements. (3) PPAR agonists can also influence transcriptional activation by upregulating the expression of transcriptional repressors such as IκB. (4) PPAR-mediated interference on the activation of members of the mitogen-activated protein kinase (MAPK) cascade influences transcription factor activation.