HISTONE ACETYLTRANSFERASES DURING THE CELL-CYCLE AND DIFFERENTIATION OF PHYSARUM-POLYCEPHALUM

The dynamic: state of histone acetylation is maintained by histone ace tyltransferases (HATs) and deacetylases. Cellular fractionation of pla smodia of Physarum polycephalum and partial purification of subcellula r fractions by chromatography revealed the existence of a cytoplasmic B-type and four nuclear A-type HATs, The cytoplasmic Benzyme was highl y specific for histone H4, causing di-acetylation of H4 in vitro. The nuclear enzymes (HAT-Al to HAT-A4) accepted all core histones as subst rates, but differed by the preference for certain histone species. Enz ymes were analyzed during the naturally synchronous cell cycle of macr oplasmodia. Each of the enzymes had its individual cell cycle activity pattern, indicating diverse functions in nuclear metabolism, When gro wing plasmodia were induced to undergo differentiation into dormant sc lerotia, an additional enzyme (HAT-AS) appeared at a late stage of scl erotization which correlated with differentiation-specific histone syn thesis and acetylation in the absence of DNA replication, When dormant sclerotia were induced to reenter the cell cycle, a further enzyme fo rm (HAT-AG) appeared during a short time period prior to the first pos t-germination mitosis, This enzyme had a strong preference for H2B, co rrelating with the overproportional in vivo acetate incorporation in H 2B, Both differentiation-associated HATs were undetectable in growing plasmodia, The results demonstrate that different functions of core hi stone acetylation are based on multiple enzyme forms that are independ ently regulated during the cell cycle, Transitions from one developmen tal stage into another are accompanied by specific enzyme forms, With respect to recent data in the literature it may be assumed that these HAT-forms are subunits of a HAT-complex whose composition changes duri ng the cell cycle and differentiation,The dynamic: state of histone ac etylation is maintained by histone acetyltransferases (HATs) and deace tylases, Cellular fractionation of plasmodia of Physarum polycephalum and partial purification of subcellular fractions by chromatography re vealed the existence of a cytoplasmic B-type and four nuclear A-type H ATs, The cytoplasmic B-enzyme was highly specific for histone H4, caus ing di-acetylation of H4 in vitro. The nuclear enzymes (HAT-A1 to HAT- A4) accepted all core histones as substrates, but differed by the pref erence for certain histone species. Enzymes were analyzed during the n aturally synchronous cell cycle of macroplasmodia. Each of the enzymes had its individual cell cycle activity pattern, indicating diverse fu nctions in nuclear metabolism, When growing plasmodia were induced to undergo differentiation into dormant sclerotia, an additional enzyme ( HAT-AS) appeared at a late stage of sclerotization which correlated wi th differentiation-specific histone synthesis and acetylation in the a bsence of DNA replication, When dormant sclerotia were induced to reen ter the cell cycle, a further enzyme form (HAT-AG) appeared during a s hort time period prior to the first post-germination mitosis, This enz yme had a strong preference for H2B, correlating with the overproporti onal in vivo acetate incorporation in H2B, Both differentiation-associ ated HATs were undetectable in growing plasmodia, The results demonstr ate that different functions of core histone acetylation are based on multiple enzyme forms that are independently regulated during the cell cycle, Transitions from one developmental stage into another are acco mpanied by specific enzyme forms, With respect to recent data in the l iterature it may be assumed that these HAT-forms are subunits of a HAT -complex whose composition changes during the cell cycle and different iation.