Two classes of histone acetylation in developing mouse mammary gland.

Mouse mammary gland explants rapidly incorporated W-acetate into the Fl, FZal, F2a2, and F3 histones. These acetylated histones were divided into two classes which were distinguished by their metabolic stability, electrophoretic mobility, and sensitivity to cycloheximide. The acetylation of the Fl and F2a2 histones was inhibited by cycloheximide, occurred only during their synthesis, and was limited to the c~amino group of the terminal serine. In contrast, the preformed F3 and F2al were acetylated on the E-NH% group of internal lysine residues. This acetate was unstable, and the histones were rapidly deacetylated. The F2b histone did not incorporate 14C-acetate. These results suggest that amino-terminal acetylation of the PI, FZal, and F2a2 histones represents a mechanism of polypeptide chain initiation in eucaryotic cells analogous to aminoterminal formylation in procaryotic cells. If acetylation of histones has a functional role by modifying the DNA-histone interaction, it is reasonable to assume that this modification must also be reversible. Since the acetylation of both Fl and F2a2 histones occurs only during their synthesis, and this acetate remains with the stable histone, it is unlikely that these proteins function in a reversible DNA association. In contrast, both the F2al and F3 histone fractions are reversibly acetylated on preformed molecules, suggesting that acetylation of these proteins could function in the control of RNA transcription.