Abstract
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.
Highlights
Activator protein-1 (AP-1) is a transcription factor comprised of Jun (c-Jun, JunB, and JunD) and Fos (c-Fos, FosB, Fra-1, and Fra-2) family members
AP-1JunD/c-Fos Has a Role in Hematopoiesis—To define the function of AP-1JunD/c-Fos in hematopoiesis, we analyzed the gene expression profile induced by AP-1JunD/c-Fos in embryonic stem cells of Xenopus animal caps explants
We provide evidence for a novel function of the transcription factor AP-1JunD/c-Fos in hematopoiesis during Xenopus development
Summary
AP-1 (activator protein-1) is a transcription factor comprised of Jun (c-Jun, JunB, and JunD) and Fos (c-Fos, FosB, Fra-1, and Fra-2) family members. The function of these dimers, the heterodimeric AP-1 comprised of JunD and c-Fos (AP-1JunD/c-Fos), has not been elucidated. Our findings identify AP-1JunD/c-Fos as a novel hematopoietic transcription factor and the requirement of AP-1JunD/c-Fos in BMP-4-induced hematopoiesis during Xenopus hematopoiesis. Activator protein-1 (AP-1) is an evolutionarily conserved bZip family transcription factor composed of Jun family members (e.g. c-Jun, JunB, and JunD) and Fos family members (e.g. c-Fos, FosB, Fra-1, and Fra-2). We provide evidence showing that AP-1JunD/c-Fos function is required for BMP-4-induced hematopoiesis. We demonstrate that BMP-4 controls AP-1JunD/c-Fos activity through transcriptional and post-translational regulation of junD during hematopoiesis
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