Chromatin Dynamics during DNA Replication

The epigenetic landscape is shaped by both gene transcription and DNA replication. To distinguish contributions of these processes, we followed the cell cycle dynamics of ten histone modifications. The modification pattern correlated with gene transcription, while changes in modifications followed DNA replication, reflecting the rates by which newly deposited histones are modified. Some marks appeared immediately upon replication (H4K16ac, H3K4me1), whereas all di/tri-methylations increased at a delay that was prolonged for low-expressing or TATA-containing genes. Notably, H3K9ac was observed as a wave ~5-6 Kb preceding the replication fork. This replication-guided H3K9ac was fully dependent on the acetyltransferase Rtt109, while deletion of Gcn5, the second H3K9 acetyltransferase, exclusively abolished expression-associated H3K9ac. Topoisomerases depletion strengthened both replication-dependent H3K9ac and the co-localization of RNA-PolII binding with the expression-associated H3K9ac, suggesting that super-helical stresses guide H3K9ac. Our results provide insights on the diverse dynamics of histone modifications during DNA replication.

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