Two distinct modes for propagation of histone PTMs across the cell cycle

Constance Alabert, Teresa K. Barth, Nazaret Reverón-Gómez, Simone Sidoli, Andreas Schmidt, Olen Jensen, Axel Imhof (Lead / Corresponding author), Anja Groth (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    277 Citations (Scopus)
    147 Downloads (Pure)

    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.

    Original languageEnglish
    Pages (from-to)585-590
    Number of pages6
    JournalGenes and Development
    Volume29
    Issue number6
    DOIs
    Publication statusPublished - 15 Mar 2015

    Keywords

    • Cell cycle
    • DNA replication
    • Epigenetics
    • Histone post-translational modifications
    • Histone recycling
    • Histone variants

    ASJC Scopus subject areas

    • Genetics
    • Developmental Biology

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