THE ORIGIN AND UTILITY OF HISTONE DEACETYLASES

A large region of two distinct yeast histone deacetylases, RPD3 and HD A1, is highly homologous to several prokaryotic enzymes that catalyze reactions involving various acetylated substrates, Proteins sharing th is homology domain are found also in many higher eukaryotes and they a ll appear to be related to the RPD3 family of histone deacetylases. In each member of the family, the 'prokaryotic homology' domain covers a lmost two thirds of the protein, with the remaining portion containing the most divergent sequences. These sequences are located at the C-te rminal region allowing for a clear definition of variants, Since the i nvolvement of deacetylase members in different distinct regulatory com plexes is now well established, the above observation suggests that th e C-terminal domain may confer specificity to different members of the family, The RPD3 histone deacetylases thus appear as members of a fam ily with a large conserved domain involved in enzymatic activity targe ted to a short C-terminal domain, which probably confers functional sp ecificity. The potential for deacetylases to be involved in multiple r egulatory pathways provides an attractive counterpoint to the role of multiple histone acetyltransferases as coactivators. (C) 1997 Federati on of European Biochemical Societies.