Activating transcription factor 2 targets c‐Fos, but not c‐Jun, in growth plate chondrocytes

Activating transcription factor 2 (ATF-2), c-Fos, and c-Jun belong to the bZIP family of transcription factors. Promoters of c-Fos, c-Jun, cyclin D1, and cyclin A are targets of ATF-2 in primary mouse chondrocytes. An ATF-2 expression vector was co-transfected with either c-Fos or c-Jun promoters in mutant ATF-2 chondrocytes in order to show by luciferase assay that ATF-2 increased promoter activity of c-Fos, but not c-Jun. Chromatin immunoprecipitation (ChIP) assays revealed that ATF-2 bound with the c-Fos promoter at the -294 cyclic AMP response element (CRE) site, but did not bind to the TPA responsive element (TRE) or activating protein-1 (AP1) sites of the c-Jun promoter. Dominant-negative (dn) c-Fos inhibited cyclin D1 promoter activity. However, dn c-Jun had minimal effect on this same promoter activity. c-Fos was capable of interactions with both the cyclin D1 CRE and AP1 sites, while c-Jun co-operated specifically with the cyclin D1 CRE site. Neither c-Fos nor c-Jun had any effect on cyclin A promoter activity. c-Fos was unable to bind to the cyclin A AP1 or CRE sites. In contrast c-Jun was competent in interactions with cyclin A AP1-2 as well as the CRE.