| First Author | Duan Z | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 12 | Pages | 8364-74 |
| PubMed ID | 24523408 | Mgi Jnum | J:212436 |
| Mgi Id | MGI:5581393 | Doi | 10.1074/jbc.M113.523456 |
| Citation | Duan Z, et al. (2014) Tudor-SN, a novel coactivator of peroxisome proliferator-activated receptor gamma protein, is essential for adipogenesis. J Biol Chem 289(12):8364-74 |
| abstractText | Adipogenesis, in which mesenchymal precursor cells differentiate into mature adipocytes, is a well orchestrated process. In the present study we identified Tudor-SN as a novel co-activator of the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma). We provide the first evidence that Tudor-SN and PPARgamma exist in the same complex. Both are up-regulated by the early factor C/EBPbeta during adipogenesis and significantly influence the regulation of PPARgamma target genes in both 3T3-L1 pre-adipocyte and mouse embryonic fibroblasts (MEF) upon exposure to a mixture of hormonal mixture. Moreover, aP2-PPARgamma response element (PPRE) interacts with both PPARgamma and Tudor-SN, and the gene transcriptional activation of PPRE-luc is enhanced by ectopic expression of Tudor-SN. Deletion of Tudor-SN protein (MEF-KO) affects but does not completely abolish the association of PPARgamma and aP2-PPRE. Loss-of-function studies further verified that Tudor-SN is required for adipogenesis, as deletion of Tudor-SN (MEF-KO) impairs dexamethasone, 3-isobutyl-1-methylxanthine, and insulin (DMI)-induced adipocyte differentiation and the expression of PPARgamma target genes, such as aP2 and adipsin. Furthermore, H3 acetylation levels were lower in MEF-KO than MEF-WT. Both HDAC1 and HDAC3 are stably associated with PPARgamma in MEF-KO, whereas only a small amount of association was observed in MEF-WT after 5 days of treatment during adipogenesis. PPARgamma requires various co-activators or co-repressors, which may dynamically associate with and regulate the higher order chromatin remodeling of the promoter region of PPARgamma-bound target genes; Tudor-SN is likely one of these co-activators. |
