title: ATF3 inhibits PPARγ-stimulated transactivation in adipocyte cells.
abstract: Previously, we reported that activating transcription factor 3 (ATF3) downregulates peroxisome proliferator activated receptor (PPARγ) gene expression and inhibits adipocyte differentiation in 3T3-L1 cells. Here, we investigated another role of ATF3 on the regulation of PPARγ activity. ATF3 inhibited PPARγ-stimulated transactivation of PPARγ responsive element (PPRE)-containing reporter or GAL4/PPARγ chimeric reporter. Thus, ATF3 effectively repressed rosiglitazone-stimulated expression of adipocyte fatty acid binding protein (aP2), PPARγ target gene, in 3T3-L1 cells. Coimmunoprecipitation and GST pulldown assay demonstrated that ATF3 interacted with PPARγ. Accordingly, ATF3 prevented PPARγ from binding to PPRE on the aP2 promoter. Furthermore, ATF3 suppressed p300-mediated transcriptional coactivation of PPRE-containing reporter. Chromatin immunoprecipitation assay showed that overexpression of ATF3 blocked both binding of PPARγ and recruitment of p300 to PPRE on aP2 promoter induced by rosiglitazone treatment in 3T3-L1 cells. Taken together, these results suggest that ATF3 interacts with PPARγ and represses PPARγ-mediated transactivation through suppression of p300-stimulated coactivation in 3T3-L1 cells, which may play a role in inhibition of adipocyte differentiation.
authors.affiliation: School of Korean Medicine, Pusan National University, #49 Busandae hak-ro, Mulguem-eup, Yangsan-si, Gyeongnam 609-735, South Korea.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Jang
authors.affiliation: School of Korean Medicine, Pusan National University, #49 Busandae hak-ro, Mulguem-eup, Yangsan-si, Gyeongnam 609-735, South Korea. Electronic address: jung0603@pusan.ac.kr.
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Jung
mesh_terms: D041721:3T3-L1 Cells; D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D017930:Genes, Reporter; D007333:Insulin Resistance; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000737:chemistry; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D050880:p300-CBP Transcription Factors
keywords: Activating transcription factor 3 (ATF3); PPARγ responsive element (PPRE); Peroxisome proliferator activated receptor (PPARγ); Transcriptional coactivation; p300