Effect of histone deacetylase inhibitors on heat shock protein gene expression during Xenopus development.

Abstract

We examined the effect of histone deacetylase inhibitors (HDIs), trichostatin A (TSA), valproic acid (VPA), and sodium butyrate (NaB) on heat shock protein (hsp) gene expression during early Xenopus laevis development. HDIs enhance histone acetylation and result in the relief of repressed chromatin domains and ultimately increase the accessibility of transcription factors to target cis-acting regulatory sites. Treatment of embryos with HDIs enhanced the heat shock-induced accumulation of hsp70 mRNA in post-midblastula stage embryos. No effect was observed with actin mRNA or other hsp70 family members including heat shock cognate 70 and immunoglobulin binding protein. Normally, hsp30 genes are not heat-inducible until the late neurula or early tailbud stage of development. Treatment with HDIs resulted in heat-induced expression of hsp30 genes at the gastrula stage with enhanced heat-induced accumulation in neurula and tailbud stages. HDI treatment alone did not induce the accumulation of hsp70 or hsp30 mRNA. Whole-mount in situ hybridization verified the RNA blot analyses and additionally revealed that TSA treatment did not result in any major alterations in the spatial pattern of stress-induced hsp70 or hsp30 mRNA accumulation in early embryos. This study suggests that the states of Xenopus hsp70 and 30 chromatin are subject to repression beyond the midblastula transition.