TrxG and PcG Proteins but Not Methylated Histones Remain Associated with DNA through Replication

Propagation of gene-expression patterns through the cell cycle requires the existence of an epigenetic mark that re-establishes the chromatin architecture of the parental cell in the daughter cells. We devised assays to determine which potential epigenetic marks associate with epigenetic maintenance elements during DNA replication in Drosophila embryos. Histone H3 trimethylated at lysines 4 or 27 is present during transcription but, surprisingly, is replaced by nonmethylated H3 following DNA replication. Methylated H3 is detected on DNA only in nuclei not in S phase. In contrast, the TrxG and PcG proteins Trithorax and Enhancer-of-Zeste, which are H3K4 and H3K27 methylases, and Polycomb continuously associate with their response elements on the newly replicated DNA. We suggest that histone modification enzymes may re-establish the histone code on newly assembled unmethylated histones and thus may act as epigenetic marks. [Display omitted] ► Parental H3K4me3 and H3K27me3 are not transferred to original sites on nascent DNA ► De novo methylation of H3 occurs only in the next G phase ► Trx, Pc, and E(z) are transiently associated with PCNA ► Trx, Pc, and E(z) are transferred to their response elements during DNA replication The replisome displaces methylated histones during DNA replication, whereas Trithorax and Polycomb proteins remain bound, suggesting that these factors are the bona fide markers for epigenetic inheritance.