FIGURE 7.

ATF-2, c-Jun, and Sp3 association with the ITGB8 core promoter requires p38 signaling. A, chromatin immunoprecipitation of ATF-2, c-Jun, or Sp3 in adult lung fibroblasts treated with the p38 inhibitor, SB202190, with PCR amplification of regions from the ITGB8 promoter (± S.E.). Genomic locations of the amplicated regions are indicated in the schematic below the graphs. Essentially identical results were obtained using antibodies against phospho-ATF-2 and total ATF-2 and thus, results were pooled. B, hypothetical model for regulation of the ITGB8 promoter by p38, ATF-2, c-Jun, and Sp3. p38 phosphorylates ATF-2, which heterodimerizes with c-Jun to bind to the CRE site in the ITGB8 core promoter. Along with Sp3, which is already bound to its cognate SP site adjacent to the CRE site in the ITGB8 core promoter, these transcription factors form a higher-order chromatin complex that interacts either directly with the P2 region or indirectly through yet unidentified transcription factors to activate transcription of ITGB8. * = p ≤ 0.05.