The highly conserved N-terminal domains of histones H3 and H4 are required for normal cell cycle progression

The N-terminal domains of the histones H3 and H4 are highly conserved throughout evolution. Mutant alleles deleted for these N-terminal domains were constructed in vitro and examined for function in vivo in Saccharomyces cerevisiae. Cells containing a single deletion allele of either histone H3 or histone H4 were viable. Deletion of the N-terminal domain of histone H4 caused cells to become sterile and temperature sensitive for growth. The normal cell cycle progression of these cells was also altered, as revealed by a major delay in progression through the G2+M periods. Deletion of the N-terminal domain of histone H3 had only minor effects on mating and the temperature-sensitive growth of mutant cells. However, like the H4 mutant, the H3 mutants had a significant delay in completing the G2+M periods of the division cycle. Double mutants containing N-terminal domain deletions of both histone H3 and histone H4 were inviable. The phenotypes of cells subject to this synthetic lethality suggest that the N-terminal domains are required for functions essential throughout the cell division cycle and provide genetic evidence that histones are randomly distributed during chromosome replication. The nucleosome consists of the four core histones H2A, H2B, H3, and H4 arranged as two H2A-H2B dimers and one H3-H4 tetramer, around which is wrapped approximatel