Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation - PubMed (original) (raw)

Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation

Anne Bugge et al. PPAR Res. 2010.

Abstract

The peroxisome proliferator-activated receptors (PPARs) are central regulators of fat metabolism, energy homeostasis, proliferation, and inflammation. The three PPAR subtypes, PPARα, β/δ, and γ activate overlapping but also very different target gene programs. This review summarizes the insights into PPAR subtype-specific transactivation provided by genome-wide studies and discusses the recent advances in the understanding of the molecular mechanisms underlying PPAR subtype specificity with special focus on the regulatory role of AF-1.

PubMed Disclaimer

Figures

Figure 1

Figure 1

The PPAR A/B-domains potentiate transactivation of the highly subtype selective target genes. Illustration of the differential requirement for the PPAR A/B-domains in the transactivation of highly subtype selective and non-subtype selective target genes. The PPAR subtype specific target genes are generally expressed at very low levels in the absence of PPARs, but expression is dramatically increased upon introduction of full length exogenous PPAR. The activities of the PPAR A/B-domains are necessary to obtain this potent induction of the highly subtype specific target genes, presumably by facilitating recruitment and tethering of histone acetylase complexes (HATs) and the Mediator complex. Conversely, non-subtype selective PPAR target genes are usually already expressed at high levels in the absence of PPARs, and their expression levels are only increased by a few fold in response to ectopic PPAR expression. The PPAR A/B-domains appear to be dispensable for transactivation of this group of target genes.

References

    1. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347(6294):645–650. - PubMed
    1. Kliewer SA, Forman BM, Blumberg B, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proceedings of the National Academy of Sciences of the United States of America. 1994;91(15):7355–7359. - PMC - PubMed
    1. Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors. Cell. 1992;68(5):879–887. - PubMed
    1. Escher P, Wahli W. Peroxisome proliferator-activated receptors: insight into multiple cellular functions. Mutation Research. 2000;448(2):121–138. - PubMed
    1. Kersten S, Desvergne B, Wahli W. Roles of PPARS in health and disease. Nature. 2000;405(6785):421–424. - PubMed

LinkOut - more resources