Multiple expression control mechanisms of peroxisome proliferator-activated receptors and their target genes.
The peroxisome proliferator-activated receptors (PPAR) alpha, beta/delta and gamma belong to the nuclear hormone receptor superfamily. As ligand-activated receptors, they form a functional transcriptional unit upon heterodimerization with retinoid X receptors (RXRs). PPARs are activated by fatty acids and their derivatives, whereas RXR is activated by 9-cis retinoic acid. This heterodimer binds to peroxisome proliferator response elements (PPRE) residing in target genes and stimulates their expression. Recent reports now indicate that PPARs and RXRs can function independently, in the absence of a hetero-partner, to modulate gene expression. Of importance, these non-canonical mechanisms underscore the impact of both cofactors and DNA on gene expression. Furthermore, these different mechanisms reveal the increasing repertoire of PPAR 'target' genes that now encompasses non-PPREs containing genes. It is also becoming apparent that understanding the regulation of PPAR expression and activity, can itself have a significant influence on how the expression of subgroups of target genes is studied and integrated in current knowledge.
Tan
Nguan Soon
NS
Center for Integrative Genomics, NCCR Frontiers in Genetics, University of Lausanne, Biology Building, CH-1015 Lausanne, Switzerland.
Michalik
Liliane
L
Desvergne
Beatrice
B
Wahli
Walter
W
D000818:Animals; D005786:Gene Expression Regulation; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
D006728:Hormones; D047492:Peroxisome Proliferator-Activated Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha