Stepwise histone modifications are mediated by multiple enzymes that rapidly associate with nascent DNA during replication

The mechanism of epigenetic inheritance following DNA replication may involve dissociation of chromosomal proteins from parental DNA and reassembly on daughter strands in a specific order. Here we investigated the behaviour of different types of chromosomal proteins using newly developed methods that allow assessment of the assembly of proteins during DNA replication. Unexpectedly, most chromatin-modifying proteins tested, including methylases, demethylases, acetyltransferases and a deacetylase, are found in close proximity to PCNA or associate with short nascent DNA. Histone modifications occur in a temporal order following DNA replication, mediated by complex activities of different enzymes. In contrast, components of several major nucleosome-remodelling complexes are dissociated from parental DNA, and are later recruited to nascent DNA following replication. Epigenetic inheritance of gene expression patterns may require many aspects of chromatin structure to remain in close proximity to the replication complex followed by reassembly on nascent DNA shortly after replication.