Histone acetylation is a checkpoint in FGF-stimulated mesoderm induction

We have previously demonstrated that the transcription factor, AP-1 (c-jun/ c-fos heterodimer), mediates fibroblast growth factor (FGF) signaling durin g mesoderm induction in Xenopus embryo. In the present studies, we show tha t histone acetylation is involved in FGF-mediated signaling leading to meso derm induction, Histone acetylation is a dynamic process regulated by the a ctivities of two histone-modifying enzymes, the histone acetyltransferase(s ) and histone deacetylase(s) (HDACs), We found that basal and FGF-regulated activator protein 1 (AP-1) activity in Xenopus embryo is markedly reduced by treatment of trichostatin A (TSA), a specific inhibitor of HDAC. However , activity of another transcription factor, NF kappa B, is enhanced by TSA treatment. AP-1-mediated mesoderm induction in the animal caps is dramatica lly suppressed by TSA at a dose-dependent manner. This suppression can be r escued by ectopic expression of HDAC3 at early stage, Finally, are found th at histone acetylation in animal caps is inhibited by FGF whereas enhanced by TSA las It control). Therefore, we propose that histone acetylation is a checkpoint for transduction of the FGF/AP-1 signals to induce mesoderm, Pu blished 2000 Wiley-Liss, Inc.dagger.