The experiments to be described are concerned with the role of histones in nuclear function, with particular emphasis on biosynthetic reactions which modify the structure of histones by the introduction of acetyl and methyl groups. These reactions have been studied in isolated calf thymus nucleiin vitro, using acetate-2-C14 and methionine-methyl-C'4 (see ref. 1) as precursors, comparing their incorporation with that of C14-lysine and other amino acids, and testing the effects of Puro-mycinon thesynthesisof different histone fractions. Evidence will be presented to show that, in the cell nucleus, the acetylation and methylation ofthe histones occur very probably after completion of the polypeptide chain. Such modifications of histone structure, acetylation in particular, may affect the capacity of the histonesto inhibit ribonucleic acid synthesis in vivo. This view is supported by the finding that, when isolated arginine-rich histones are subjected to a limited acetylation, they lose much of their effectiveness as inhibitors of RNA synthesis by the DNA-dependent RNA polymerases of calf thymus nuclei or Escherichia coli. Yet, such modified histones are still strongly basic proteins which retain an affinity for DNA comparable to that of the parent histone from which they were derived.

The findings introduce the possibility that histone effects on nuclear RNA me-tabolism may involve more than a simpleinhibition of RNA synthesis, and that more subtle mechanisms may exist which permit both inhibition and reactivation of RNA production at different loci along the chromosome. Interest in the histones as regulators of chromosomal activity has heightened considerably in the past few years, as increasing experimental evidence has ac-cumulated to support the view that the role of histones is to inhibit chromosomal