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

Molecular Cell
Nazaret Reverón-GómezAnja Groth

Abstract

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.

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Datasets Mentioned

BETA
GSM923449
GSM733696
GSM733682
GSM1003520
GSM958735
GSM788633
GSE110354

Methods Mentioned

BETA
ChOR-seq
immunoprecipitation
pull-down
ChIP-seq
pull-downs
FACS
RNA-seq
proximity-ligation
PCR
ChIPs

Software Mentioned

MACS
UCSC LiftOver
Galaxy
custom
Hilbertvis
Seqplot
seq
qChOR
R scripts
Bowtie

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