title: Two distinct modes for propagation of histone PTMs across the cell cycle.
abstract: Epigenetic states defined by chromatin can be maintained through mitotic cell division. However, it remains unknown how histone-based information is transmitted. Here we combine nascent chromatin capture (NCC) and triple-SILAC (stable isotope labeling with amino acids in cell culture) labeling to track histone modifications and histone variants during DNA replication and across the cell cycle. We show that post-translational modifications (PTMs) are transmitted with parental histones to newly replicated DNA. Di- and trimethylation marks are diluted twofold upon DNA replication, as a consequence of new histone deposition. Importantly, within one cell cycle, all PTMs are restored. In general, new histones are modified to mirror the parental histones. However, H3K9 trimethylation (H3K9me3) and H3K27me3 are propagated by continuous modification of parental and new histones because the establishment of these marks extends over several cell generations. Together, our results reveal how histone marks propagate and demonstrate that chromatin states oscillate within the cell cycle.
authors: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark;
authors: Constance
authors: C
authors: Alabert
authors: Munich Centre of Integrated Protein Science, Ludwig-Maximillians University of Munich, 80336 Munich, Germany; Adolf Butenandt Institute, Ludwig-Maximillians University of Munich, 80336 Munich, Germany;
authors: Teresa K
authors: TK
authors: Barth
authors: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark;
authors: Nazaret
authors: N
authors: Reverón-Gómez
authors: Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Simone
authors: S
authors: Sidoli
authors: Munich Centre of Integrated Protein Science, Ludwig-Maximillians University of Munich, 80336 Munich, Germany; Adolf Butenandt Institute, Ludwig-Maximillians University of Munich, 80336 Munich, Germany;
authors: Andreas
authors: A
authors: Schmidt
authors: Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Ole N
authors: ON
authors: Jensen
authors: Munich Centre of Integrated Protein Science, Ludwig-Maximillians University of Munich, 80336 Munich, Germany; Adolf Butenandt Institute, Ludwig-Maximillians University of Munich, 80336 Munich, Germany; imhof@lmu.de anja.groth@bric.ku.dk.
authors: Axel
authors: A
authors: Imhof
authors: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark; imhof@lmu.de anja.groth@bric.ku.dk.
authors: Anja
authors: A
authors: Groth
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D004261:DNA Replication; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D017434:Protein Structure, Tertiary
chemical_list: D002843:Chromatin; D006657:Histones
keywords: DNA replication; cell cycle; epigenetics; histone post-translational modifications; histone recycling; histone variants