1. Developmental Biology
  2. Chromosomes and Gene Expression
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Spatiotemporal coupling and decoupling of gene transcription with DNA replication origins during embryogenesis in C. elegans

  1. Ehsan M Pourkarimi
  2. James M Bellush
  3. Iestyn Whitehouse  Is a corresponding author
  1. Memorial Sloan Kettering Cancer Center, United States
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Cite this article as: eLife 2016;5:e21728 doi: 10.7554/eLife.21728

Abstract

The primary task of developing embryos is genome replication, yet how DNA replication is integrated with the profound cellular changes that occur through development is largely unknown. Using an approach to map DNA replication at high resolution in C. elegans, we show that replication origins are marked with specific histone modifications that define gene enhancers. We demonstrate that the level of enhancer associated modifications scale with the efficiency at which the origin is utilized. By mapping replication origins at different developmental stages, we show that the positions and activity of origins is largely invariant through embryogenesis. Contrary to expectation, we find that replication origins are specified prior to the broad onset of zygotic transcription, yet when transcription initiates it does so in close proximity to the pre-defined replication origins. Transcription and DNA replication origins are correlated, but the association breaks down when embryonic cell division ceases. Collectively, our data indicate that replication origins are fundamental organizers and regulators of gene activity through embryonic development.

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Author details

  1. Ehsan M Pourkarimi

    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9598-3465

  2. James M Bellush

    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Iestyn Whitehouse

    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    For correspondence
    whitehoi@mskcc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0385-3116

Funding

National Institutes of Health (GM102253)

  • Iestyn Whitehouse

Memorial Sloan-Kettering Cancer Center (P30CA008748)

  • Iestyn Whitehouse

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Michael R Botchan, University of California, Berkeley, United States

Publication history

  1. Received: September 21, 2016
  2. Accepted: December 22, 2016
  3. Accepted Manuscript published: December 23, 2016 (version 1)
  4. Accepted Manuscript updated: December 28, 2016 (version 2)
  5. Version of Record published: January 9, 2017 (version 3)

Copyright

© 2016, Pourkarimi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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