Sodium butyrate In millimolar concentrations causes an accumulation of acetylated histone species In a variety of vertebrate cell lines. In all lines tested, butyrate caused hyperacetylatlon of H3 and H4, and In rat IRC8 cells, H2A and H2B were also affected. In Friend erythroleukrtmic cells, butyrate also induces the synthesis of a nonhlstone chromosome1 protein, IPzs. Butyrate does not affect the rate of histone acetylation in cell-free extracts or nuclei of Friend cells. Rather, this fatty acid inhibits histone deacetylation. Cellfree extracts of either control cells or butyrategrown cells contain comparable levels of histonedeacetylating activity. This in vitro activity is inhibited by the addition of butyrate to the extracts. Thus butyrate appears to be an inhibitor of histone deacetylases both In vivo and in vitro.