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

We examine the potential role of histone hyperacetylation in gene acti vation during Xenopus development using Trichostatin A, (TSA), a speci fic inhibitor of histone deacetylase. We find that TSA is very effecti ve in inducing both core histone hyperacetylation and histone H1 degre es gene expression in a Xenopus somatic cell line. In contrast, TSA do es not induce histone hyperacetylation or histone H1 degrees transcrip tion in Xenopus oocytes. Histone hyperacetylation is developmentally r egulated during Xenopus embryogenesis; hyperacetylated histones first accumulate early in gastrulation. The capacity of TSA to induce histon e H1 degrees gene expression correlates with the induction of histone hyperacetylation. Concentrations of TSA sufficient to induce histone h yperacetylation in Xenopus embryos delay gastrulation and cause dimini shed 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 sufficien t for early morphogenesis it has a role in establishing stable states of differential gene activity during gastrulation. (C) 1994 Academic P ress, Inc.