title: Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation.
abstract: The nucleosome is the fundamental unit of assembly of the chromosome and reversible modifications of the histones have been suggested to be important in many aspects of nucleosome function. The structure-function relations of the amino-terminal domain of yeast histone H4 were examined by the creation of directed point mutations. The four lysines subject to reversible acetylation were essential for histone function as the substitution of arginine or asparagine at these four positions was lethal. No single lysine residue was completely essential since arginine substitutions at each position were viable, although several of these mutants were slower in completing DNA replication. The simultaneous substitution of glutamine for the four lysine residues was viable but conferred several phenotypes including mating sterility, slow progression through the G2/M period of the division cycle, and temperature-sensitive growth, as well as a prolonged period of DNA replication. These results provide genetic proof for the roles of the H4 amino-terminal domain lysines in gene expression, replication, and nuclear division.
authors.affiliation: Department of Microbiology, School of Medicine, University of Virginia, Charlottesville 22908.
authors.forename: P C
authors.initials: PC
authors.lastname: Megee
authors.forename: B A
authors.initials: BA
authors.lastname: Morgan
authors.forename: B A
authors.initials: BA
authors.lastname: Mittman
authors.forename: M M
authors.initials: MM
authors.lastname: Smith
mesh_terms: D000107:Acetylation; D000483:Alleles; D002453:Cell Cycle; D002872:Chromosome Deletion; D003062:Codon / Q000235:genetics; D005973:Glutamine; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D008239:Lysine; D009154:Mutation; D010957:Plasmids; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*
chemical_list: D003062:Codon; D006657:Histones; D005973:Glutamine; D008239:Lysine