Chromatin dynamics during DNA replication

Genome Res. 2016 Sep;26(9):1245-56. doi: 10.1101/gr.201244.115. Epub 2016 May 25.


Chromatin is composed of DNA and histones, which provide a unified platform for regulating DNA-related processes, mostly through their post-translational modification. During DNA replication, histone arrangement is perturbed, first to allow progression of DNA polymerase and then during repackaging of the replicated DNA. To study how DNA replication influences the pattern of histone modification, we followed the cell-cycle dynamics of 10 histone marks in budding yeast. We find that histones deposited on newly replicated DNA are modified at different rates: While some marks appear immediately upon replication (e.g., H4K16ac, H3K4me1), others increase with transcription-dependent delays (e.g., H3K4me3, H3K36me3). Notably, H3K9ac was deposited as a wave preceding the replication fork by ∼5-6 kb. This replication-guided H3K9ac was fully dependent on the acetyltransferase Rtt109, while expression-guided H3K9ac was deposited by Gcn5. Further, topoisomerase depletion intensified H3K9ac in front of the replication fork and in sites where RNA polymerase II was trapped, suggesting supercoiling stresses trigger H3K9 acetylation. Our results assign complementary roles for DNA replication and gene expression in defining the pattern of histone modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Chromatin
  • DNA Replication / genetics*
  • DNA-Directed DNA Polymerase / genetics
  • Histone Acetyltransferases / genetics*
  • Histone Code / genetics*
  • Histone-Lysine N-Methyltransferase / genetics
  • Histones
  • RNA Polymerase II / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomycetales / genetics


  • Chromatin
  • Histones
  • Saccharomyces cerevisiae Proteins
  • Histone-Lysine N-Methyltransferase
  • GCN5 protein, S cerevisiae
  • Histone Acetyltransferases
  • Rtt109 protein, S cerevisiae
  • RNA Polymerase II
  • DNA-Directed DNA Polymerase