The Methylation of Histones during Regeneration of the Liver

Abstract

Abstract Histones are methylated after synthesis by a transfer of methyl groups (derived from methionine) to the free e-amino groups of lysine residues in the polypeptide chain. The time courses of histone synthesis and methylation have been compared during regeneration of the liver in the rat. Uniformly labeled arginine-14C and methionine-(methyl-14C) were used as precursors, and the e-N-methyllysines were separated from the other amino acids in the protein digest. The histones were fractionated by differential acetone precipitation to yield an arginine-rich fraction containing 0.91 mole per 100 moles of e-N-methyllysines. e-N-Dimethyllysine is the predominant form of the modified amino acid. Its concentration exceeds that of the monomethyl derivative by a factor of 3. Histone methylation is a relatively late event in the course of cell division after partial hepatectomy. The peak in methylation occurs at a time when the rates of histone synthesis and DNA synthesis have already begun to decline. Methylation of histones does not correlate with an increase in DNA template activity for RNA synthesis, nor with the initiation of histone, nonhistone protein, or DNA synthesis. It may correlate with structural and functional changes known to occur in the nucleus prior to mitosis, which involve a condensation of the chromatin and a curtailment of nucleic acid synthesis.