GENE-EXPRESSION WITHIN A CHROMATIN DOMAIN - THE ROLE OF CORE HISTONE HYPERACETYLATION

Scaffold-attached regions (SAR elements) increase transcriptional rates for integrated but not episomal templates, and this effect can be potentiated by using an epigenetically active reagent, butyrate. The action of butyrate is a direct one, not involving de novo protein synthesis, and can be mimicked by using a novel and highly specific inhibitor of histone deacetylases, (R)-trichostatin A. This leads to a model in which SAR elements serve to stabilize the chromosomal topology arising as a consequence of hyperacetylation of histone cores. The synergistic effects of histone hyperacetylation and SARs are mediated by promoter upstream elements since, for a simple TATA box, the response to both parameters is an additive one.