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Histone acetylation controls the inactive X chromosome replication dynamics

Author

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  • Corella S. Casas-Delucchi

    (Technische Universität Darmstadt
    Max Delbrück Center for Molecular Medicine)

  • Alessandro Brero

    (Max Delbrück Center for Molecular Medicine)

  • Hans-Peter Rahn

    (Max Delbrück Center for Molecular Medicine)

  • Irina Solovei

    (Center for Integrated Protein Science, Ludwig Maximilians University Munich, Planegg-Martinsried, Munich 82152, Germany.)

  • Anton Wutz

    (Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, CB2 1QR, UK.)

  • Thomas Cremer

    (Center for Integrated Protein Science, Ludwig Maximilians University Munich, Planegg-Martinsried, Munich 82152, Germany.)

  • Heinrich Leonhardt

    (Center for Integrated Protein Science, Ludwig Maximilians University Munich, Planegg-Martinsried, Munich 82152, Germany.)

  • M. Cristina Cardoso

    (Technische Universität Darmstadt
    Max Delbrück Center for Molecular Medicine)

Abstract

In mammals, dosage compensation between male and female cells is achieved by inactivating one female X chromosome (Xi). Late replication of Xi was proposed to be involved in the maintenance of its silenced state. Here, we show a highly synchronous replication of the Xi within 1 to 2 h during early-mid S-phase by following DNA replication in living mammalian cells with green fluorescent protein-tagged replication proteins. The Xi was replicated before or concomitant with perinuclear or perinucleolar facultative heterochromatin and before constitutive heterochromatin. Ectopic expression of the X-inactive-specific transcript (Xist) gene from an autosome imposed the same synchronous replication pattern. We used mutations and chemical inhibition affecting different epigenetic marks as well as inducible Xist expression and we demonstrate that histone hypoacetylation has a key role in controlling Xi replication. The epigenetically controlled, highly coordinated replication of the Xi is reminiscent of embryonic genome replication in flies and frogs before genome activation and might be a common feature of transcriptionally silent chromatin.

Suggested Citation

  • Corella S. Casas-Delucchi & Alessandro Brero & Hans-Peter Rahn & Irina Solovei & Anton Wutz & Thomas Cremer & Heinrich Leonhardt & M. Cristina Cardoso, 2011. "Histone acetylation controls the inactive X chromosome replication dynamics," Nature Communications, Nature, vol. 2(1), pages 1-11, September.
  • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1218
    DOI: 10.1038/ncomms1218
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    Cited by:

    1. María Arroyo & Florian D. Hastert & Andreas Zhadan & Florian Schelter & Susanne Zimbelmann & Cathia Rausch & Anne K. Ludwig & Thomas Carell & M. Cristina Cardoso, 2022. "Isoform-specific and ubiquitination dependent recruitment of Tet1 to replicating heterochromatin modulates methylcytosine oxidation," Nature Communications, Nature, vol. 13(1), pages 1-28, December.

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