The PPARgamma2 A/B-domain plays a gene-specific role in transactivation and cofactor recruitment
- PMID: 19282365
- PMCID: PMC5419289
- DOI: 10.1210/me.2008-0236
The PPARgamma2 A/B-domain plays a gene-specific role in transactivation and cofactor recruitment
Abstract
We have previously shown that adenoviral expression of peroxisome proliferator-activated receptors (PPARs) leads to rapid establishment of transcriptionally active complexes and activation of target gene expression within 5-8 h after transduction. Here we have used the adenoviral delivery system combined with expression array analysis to identify novel putative PPARgamma target genes in murine fibroblasts and to determine the role of the A/B-domain in PPARgamma-mediated transactivation of genomic target genes. Of the 257 genes found to be induced by PPARgamma2 expression, only 25 displayed A/B-domain dependency, i.e. significantly reduced induction in the cells expressing the truncated PPARgamma lacking the A/B-domain (PPARgammaCDE). Nine of the 25 A/B-domain-dependent genes were involved in lipid storage, and in line with this, triglyceride accumulation was considerably decreased in the cells expressing PPARgammaCDE compared with cells expressing full-length PPARgamma2. Using chromatin immunoprecipitation, we demonstrate that PPARgamma binding to genomic target sites and recruitment of the mediator component TRAP220/MED1/PBP/DRIP205 is not affected by the deletion of the A/B-domain. By contrast, the PPARgamma-mediated cAMP response element-binding protein (CREB)-binding protein (CBP) and p300 recruitment to A/B-domain-dependent target genes is compromised by deletion of the A/B-domain. These results indicate that the A/B-domain of PPARgamma2 is specifically involved in the recruitment or stabilization of CBP- and p300-containing cofactor complexes to a subset of target genes.
Figures
![Fig. 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5419289/bin/zmg0060944420001.gif)
![Fig. 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5419289/bin/zmg0060944420002.gif)
![Fig. 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5419289/bin/zmg0060944420003.gif)
![Fig. 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5419289/bin/zmg0060944420004.gif)
![Fig. 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5419289/bin/zmg0060944420005.gif)
![Fig. 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5419289/bin/zmg0060944420006.gif)
![Fig. 7.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5419289/bin/zmg0060944420007.gif)
![Fig. 8.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5419289/bin/zmg0060944420008.gif)
![Fig. 9.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5419289/bin/zmg0060944420009.gif)
Similar articles
-
MED14 tethers mediator to the N-terminal domain of peroxisome proliferator-activated receptor gamma and is required for full transcriptional activity and adipogenesis.Mol Cell Biol. 2010 May;30(9):2155-69. doi: 10.1128/MCB.01238-09. Epub 2010 Mar 1. Mol Cell Biol. 2010. PMID: 20194623 Free PMC article.
-
Transcription coactivator PBP, the peroxisome proliferator-activated receptor (PPAR)-binding protein, is required for PPARalpha-regulated gene expression in liver.J Biol Chem. 2004 Jun 4;279(23):24427-34. doi: 10.1074/jbc.M402391200. Epub 2004 Mar 29. J Biol Chem. 2004. PMID: 15150259
-
Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor gamma-stimulated adipogenesis and target gene expression.Mol Cell Biol. 2008 Feb;28(3):1081-91. doi: 10.1128/MCB.00967-07. Epub 2007 Nov 26. Mol Cell Biol. 2008. PMID: 18039840 Free PMC article.
-
Transcriptional coactivator PRIP, the peroxisome proliferator-activated receptor gamma (PPARgamma)-interacting protein, is required for PPARgamma-mediated adipogenesis.J Biol Chem. 2003 Jul 11;278(28):25281-4. doi: 10.1074/jbc.C300175200. Epub 2003 May 16. J Biol Chem. 2003. PMID: 12754253
-
Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation.J Biol Chem. 2002 May 31;277(22):20011-9. doi: 10.1074/jbc.M201739200. Epub 2002 Mar 23. J Biol Chem. 2002. PMID: 11912212
Cited by
-
The Role of PPARs in Breast Cancer.Cells. 2022 Dec 28;12(1):130. doi: 10.3390/cells12010130. Cells. 2022. PMID: 36611922 Free PMC article. Review.
-
PPAR-γ Partial Agonists in Disease-Fate Decision with Special Reference to Cancer.Cells. 2022 Oct 13;11(20):3215. doi: 10.3390/cells11203215. Cells. 2022. PMID: 36291082 Free PMC article. Review.
-
Isoform-specific functions of PPARγ in gene regulation and metabolism.Genes Dev. 2022 Mar 1;36(5-6):300-312. doi: 10.1101/gad.349232.121. Epub 2022 Mar 10. Genes Dev. 2022. PMID: 35273075 Free PMC article.
-
LPIN1 promotes triglycerides synthesis and is transcriptionally regulated by PPARG in buffalo mammary epithelial cells.Sci Rep. 2022 Feb 11;12(1):2390. doi: 10.1038/s41598-022-06114-w. Sci Rep. 2022. PMID: 35149744 Free PMC article.
-
Peroxisome proliferator-activated receptor γ isoforms differentially regulate preadipocyte proliferation, apoptosis, and differentiation in chickens.Poult Sci. 2020 Dec;99(12):6410-6421. doi: 10.1016/j.psj.2020.09.086. Epub 2020 Oct 8. Poult Sci. 2020. PMID: 33248556 Free PMC article.
References
-
- Escher P, Wahli W2000. Peroxisome proliferator-activated receptors: insight into multiple cellular functions. Mutat Res 448:121–138 - PubMed
-
- Bishop-Bailey D, Wray J2003. Peroxisome proliferator-activated receptors: a critical review on endogenous pathways for ligand generation. Prostaglandins Other Lipid Mediat 71:1–22 - PubMed
-
- Xu HE, Lambert MH, Montana VG, Plunket KD, Moore LB, Collins JL, Oplinger JA, Kliewer SA, Gampe Jr RT, McKee DD, Moore JT, Willson TM2001. Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA 98:13919–13924 - PMC - PubMed
-
- Kersten S, Desvergne B, Wahli W2000. Roles of PPARs in health and disease. Nature 405:421–424 - PubMed
-
- Chevillotte E, Rieusset J, Roques M, Desage M, Vidal H2001. The regulation of uncoupling protein-2 gene expression by ω-6 polyunsaturated fatty acids in human skeletal muscle cells involves multiple pathways, including the nuclear receptor peroxisome proliferator-activated receptor β. J Biol Chem 276:10853–10860 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous