Author:
Alabert Constance,Barth Teresa K.,Reverón-Gómez Nazaret,Sidoli Simone,Schmidt Andreas,Jensen Ole N.,Imhof Axel,Groth Anja
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.
Funder
European Research Council
Danish National Research Foundation
Danish Cancer Society
Lundbeck Foundation
European Union
German Research Council
Human Frontier Science Program
Danish Medical Research Council
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
330 articles.
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