1. Developmental Biology
  2. Genetics and Genomics
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Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices

  1. Claudia Racioppi  Is a corresponding author
  2. Keira A Wiechecki
  3. Lionel Christiaen  Is a corresponding author
  1. New York University, United States
Research Article
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Cite this article as: eLife 2019;8:e49921 doi: 10.7554/eLife.49921

Abstract

During embryogenesis, chromatin accessibility profiles control lineage-specific gene expression by modulating transcription, thus impacting multipotent progenitor states and subsequent fate choices. Subsets of cardiac and pharyngeal/head muscles share a common origin in the cardiopharyngeal mesoderm, but the chromatin landscapes that govern multipotent progenitors competence and early fate choices remain largely elusive. Here, we leveraged the simplicity of the chordate model Ciona to profile chromatin accessibility through stereotyped transitions from naive Mesp+ mesoderm to distinct fate-restricted heart and pharyngeal muscle precursors. An FGF-Foxf pathway acts in multipotent progenitors to establish cardiopharyngeal-specific patterns of accessibility, which govern later heart vs. pharyngeal muscle-specific expression profiles, demonstrating extensive spatiotemporal decoupling between early cardiopharyngeal enhancer accessibility and late cell-type-specific activity. We found that multiple cis-regulatory elements, with distinct chromatin accessibility profiles and motif compositions, are required to activate Ebf and Tbx1/10, two key determinants of cardiopharyngeal fate choices. We propose that these 'combined enhancers' foster spatially and temporally accurate fate choices, by increasing the repertoire of regulatory inputs that control gene expression, through either accessibility and/or activity.

Article and author information

Author details

  1. Claudia Racioppi

    Center for Developmental Genetics, Department of Biology, New York University, New York, United States
    For correspondence
    cr1636@nyu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8117-1124
  2. Keira A Wiechecki

    Center for Developmental Genetics, Department of Biology, New York University, 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:" 0000-0003-0572-6284
  3. Lionel Christiaen

    Center for Developmental Genetics, Department of Biology, New York University, New York, United States
    For correspondence
    lc121@nyu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5930-5667

Funding

European Molecular Biology Organization (Long Term Fellowship)

  • Claudia Racioppi

National Heart, Lung, and Blood Institute (R01 HL108643)

  • Lionel Christiaen

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD096770)

  • Lionel Christiaen

Leducq Foundation (15CVD01)

  • Lionel Christiaen

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

Reviewing Editor

  1. Brad Davidson, Swarthmore College, United States

Publication history

  1. Received: July 4, 2019
  2. Accepted: November 18, 2019
  3. Accepted Manuscript published: November 20, 2019 (version 1)

Copyright

© 2019, Racioppi 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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