Accurate Recycling of Parental Histones Reproduces the Histone Modification Landscape during DNA Replication

• Published in: Molecular cell Vol. 72; no. 2; pp. 239 - 249.e5
• Main Authors: Reverón-Gómez, Nazaret, González-Aguilera, Cristina, Stewart-Morgan, Kathleen R., Petryk, Nataliya, Flury, Valentin, Graziano, Simona, Johansen, Jens Vilstrup, Jakobsen, Janus Schou, Alabert, Constance, Groth, Anja
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.10.2018; Cell Press
• Subjects: cell cycle; ChOR-seq; chromatin replication; DNA; DNA replication; epigenetics; epigenome maintenance; H3K27me3; H3K4me3; histone modification; histone recycling; histones; landscapes; methylation; nucleosomes; post-translational modification; quantitative ChIP-seq; histone modification; cell cycle; ChOR-seq; H3K4me3; quantitative ChIP-seq; histone recycling; epigenome maintenance; epigenetics; chromatin replication; H3K27me3
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2018.08.010

Chromatin organization is disrupted genome-wide during DNA replication. On newly synthesized DNA, nucleosomes are assembled from new naive histones and old modified histones. It remains unknown whether the landscape of histone post-translational modifications (PTMs) is faithfully copied during DNA replication or the epigenome is perturbed. Here we develop chromatin occupancy after replication (ChOR-seq) to determine histone PTM occupancy immediately after DNA replication and across the cell cycle. We show that H3K4me3, H3K36me3, H3K79me3, and H3K27me3 positional information is reproduced with high accuracy on newly synthesized DNA through histone recycling. Quantitative ChOR-seq reveals that de novo methylation to restore H3K4me3 and H3K27me3 levels occurs across the cell cycle with mark- and locus-specific kinetics. Collectively, this demonstrates that accurate parental histone recycling preserves positional information and allows PTM transmission to daughter cells while modification of new histones gives rise to complex epigenome fluctuations across the cell cycle that could underlie cell-to-cell heterogeneity. [Display omitted] •ChOR-seq determines histone PTM occupancy on newly replicated DNA•Histone PTM positional information is preserved through parental histone recycling•Parental H3K27me3 domains are stable and inherited to daughter cells•Restoration of histone PTM levels follows mark- and locus-specific kinetics Histone modifications are a core component of the epigenome. Reverón-Gómez et al. develop ChOR-seq to profile histone modifications after DNA replication and find that the genomic localization of modified parental histones is preserved on daughter strands while new histone modification to restore pre-replication levels follows mark- and locus-specific kinetics.