The role of heterodimeric AP-1 protein comprised of JunD and c-Fos proteins in hematopoiesis

Activator protein-1 (AP-1) regulates a wide range of cellular processes including proliferation, differentiation, and apoptosis. As a transcription factor, AP-1 is commonly found as a heterodimer comprised of c-Jun and c-Fos proteins. However, other heterodimers may also be formed. The function of these dimers, specifically the heterodimeric AP-1 comprised of JunD and c-Fos (AP-1^JunD/c-Fos), has not been elucidated. Here, we identified a function of AP-1^JunD/c-Fos in Xenopus hematopoiesis. A gain-of-function study performed by overexpressing junD and c-fos and a loss-of-function study using morpholino junD demonstrate a critical role for AP-1^JunD/c-Fos in hematopoiesis during Xenopus embryogenesis. Additionally, we confirmed that JunD of AP-1^JunD/c-Fos is required for BMP-4-induced hematopoiesis. We also demonstrated that BMP-4 regulated JunD activity at the transcriptional regulation and post-translational modification levels. Collectively, our findings identify AP-1^JunD/c-Fos as a novel hematopoietic transcription factor and the requirement of AP-1 ^JunD/c-Fos in BMP-4-induced hematopoiesis during Xenopus hematopoiesis.