HISTONE ACETYLATION INFLUENCES BOTH GENE-EXPRESSION AND DEVELOPMENT OF XENOPUS-LAEVIS

We examine the potential role of histone hyperacetylation in gene activation during Xenopus development using Trichostatin A, (TSA), a specific inhibitor of histone deacetylase. We find that TSA is very effective in inducing both core histone hyperacetylation and histone H1 degrees gene expression in a Xenopus somatic cell line. In contrast, TSA does not induce histone hyperacetylation or histone H1 degrees transcription in Xenopus oocytes. Histone hyperacetylation is developmentally regulated during Xenopus embryogenesis; hyperacetylated histones first accumulate early in gastrulation. The capacity of TSA to induce histone H1 degrees gene expression correlates with the induction of histone hyperacetylation. Concentrations of TSA sufficient to induce histone hyperacetylation in Xenopus embryos delay gastrulation and cause diminished midtrunk and posterior formation, suggesting defects in mesoderm formation. Although the constitutive hyperacetylation of the histones does not prevent either the cell division or differentiation sufficient for early morphogenesis it has a role in establishing stable states of differential gene activity during gastrulation. (C) 1994 Academic Press, Inc.