Two of the three major objectives of the research program supported by this grant remain unchanged from the original proposal. The first of these involves the use of a combination of biochemical and genetic approaches to decipher the biological role of histone acetylation in higher eukaryotes. The second objective is to uncover some of the molecular details of the process whereby positional information is imparted to cells during embryogenesis, using as a model system the specification of anterio-posterior position by the "zone of polarizing activity" (ZPA) in the early chick limb bud. A newer objective concerns determining the biological role of mammalian type II DNA topoisomerases, new enzymes recently discovered in this laboratory which we suspect are intimately involved in the initiation of eukaryotic DNA replication.