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 during mesoderm induction in Xenopus embryo. In the present studies, we show that histone acetylation is involved in FGF-mediated signaling leading to mesoderm induction. Histone acetylation is a dynamic process regulated by the activities 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, NFkappaB, is enhanced by TSA treatment. AP-1-mediated mesoderm induction in the animal caps is dramatically suppressed by TSA at a dose-dependent manner. This suppression can be rescued by ectopic expression of HDAC3 at early stage. Finally, we found that histone acetylation in animal caps is inhibited by FGF whereas enhanced by TSA (as a control). Therefore, we propose that histone acetylation is a checkpoint for transduction of the FGF/AP-1 signals to induce mesoderm. Published 2000 Wiley-Liss, Inc.
Xu
R H
RH
WiCell Research Institute, Wisconsin Alumni Research Foundation, University of Wisconsin, Madison, Wisconsin 53705-7365, USA. rxu@facstaff.wisc.edu
Peng
Y
Y
Fan
J
J
Yan
D
D
Yamagoe
S
S
Princler
G
G
Sredni
D
D
Ozato
K
K
Kung
H F
HF
D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008648:Mesoderm / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014161:Transduction, Genetic; D014981:Xenopus / Q000196:embryology
D004791:Enzyme Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D016328:NF-kappa B; D018808:Transcription Factor AP-1; C012589:trichostatin A; D005346:Fibroblast Growth Factors; D006655:Histone Deacetylases