Histone acetylation is a checkpoint in FGF-stimulated mesoderm induction

Ren He Xu, Ying Peng, Jing Fan, Donghong Yan, Satoshi Yamagoe, Gerald Princler, Dvora Sredni, Keiko Ozato, Hsiang Fu Kung

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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, NFκB, 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.

Original languageEnglish
Pages (from-to)628-635
Number of pages8
JournalDevelopmental Dynamics
Volume218
Issue number4
DOIs
StatePublished - Aug 2000

Funding

FundersFunder number
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentZ01HD001310

    Keywords

    • Acetylation
    • Activator protein 1
    • Embryo
    • FGF
    • Histone
    • Mesoderm
    • Trichostatin A
    • Xenopus

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