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External application of 10 rig/ml (R)-trichostatin A (TSA), a potent and specific inhibitor of mammalian histone deacetylase, to the embryo of the starfish Asterina pectinifera inhibited development during the early gastrula stage before formation of mesenchyme cells. The TSA-sensitive period was limited to the mid-blastula stage before hatching. The pulse-chase experiment clearly demonstrated that TSA induced an accumulation of acetylated histone species in blastulae through inhibition of historic deacetylation. Similar blockage of development at the early gastrula stage was observed with n-butyrate, which has been known as a weak inhibitor of historic deacetylase. These results suggest an intimate role for historic acetylation-deacetylation equilibria in starfish development.

The effects of trichostatin A (TSA), a potent and specific inhibitor of mammalian histone deacetylase, on mouse teratocarcinoma cell (F9) differentiation were investigated. TSAcaused marked changes in the morphology of cells and stimulated the production of plasminogen activator within 24hr depending on de novo synthesis of RNAand protein. During the initial 6hr of incubation, a significant accumulation of hyperacetylated histone species was observed. These results suggest that histone acetylation due to inhibition of the deacetylase is involved in the early stage of morphological and biological differentiation induced by TSA.