Inheritance of Histones H3 and H4 during DNA Replication In Vitro

Abstract

Nucleosomes are believed to carry epigenetic information through the cell cycle, including through DNA replication. It has been known for decades that parental histones are reassembled on newly replicated chromatin, but the mechanisms underlying histone inheritance and dispersal during DNA replication are not fully understood. We monitored the fate of histones H3 or H4 from a single nucleosome through DNA replication in two in vitro systems. In the SV40 system, histones assembled on a single nucleosome positioning sequence can be inherited by their own daughter DNA but are dispersed from their original location. In Xenopus laevis extracts, histones are dynamic, and nucleosomes are repositioned independent of and prior to DNA replication. Nevertheless, a high fraction of histones H3 and H4 that are inherited through DNA replication remains near its starting location. Thus, inheritance of histone proteins and their dispersal can be mechanistically uncoupled. Chromatin-based information, including that carried by histones, must be copied when DNA is replicated. By tracking histones H3 or H4 from a single nucleosome through DNA replication in two in vitro systems, Madamba et al. identify two modes of histone inheritance, one of which preserves genomic positioning information.