TY - JOUR
T1 - Accurate Recycling of Parental Histones Reproduces the Histone Modification Landscape during DNA Replication
AU - Reverón-Gómez, Nazaret
AU - González-Aguilera, Cristina
AU - Stewart-Morgan, Kathleen R.
AU - Petryk, Nataliya
AU - Flury, Valentin
AU - Graziano, Simona
AU - Johansen, Jens Vilstrup
AU - Jakobsen, Janus Schou
AU - Alabert, Constance
AU - Groth, Anja
PY - 2018/10/18
Y1 - 2018/10/18
N2 - 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. 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.
AB - 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. 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.
KW - cell cycle
KW - ChOR-seq
KW - chromatin replication
KW - epigenetics
KW - epigenome maintenance
KW - H3K27me3
KW - H3K4me3
KW - histone modification
KW - histone recycling
KW - quantitative ChIP-seq
UR - http://www.scopus.com/inward/record.url?scp=85055072338&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2018.08.010
DO - 10.1016/j.molcel.2018.08.010
M3 - Article
C2 - 30146316
AN - SCOPUS:85055072338
VL - 72
SP - 239-249.e5
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 2
ER -
