Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation

  1. Pengfei Xu
  2. Haoze V Yu
  3. Kuo-Chang Tseng
  4. Mackenzie Flath
  5. Peter Fabian
  6. Neil Segil
  7. J Gage Crump  Is a corresponding author
  1. Keck School of Medicine of University of Southern California, United States

Abstract

The specification of cartilage requires Sox9, a transcription factor with broad roles for organogenesis outside the skeletal system. How Sox9 and other factors gain access to cartilage-specific cis-regulatory regions during skeletal development was unknown. By analyzing chromatin accessibility during the differentiation of neural crest cells into chondrocytes of the zebrafish head, we find that cartilage-associated chromatin accessibility is dynamically established. Cartilage-associated regions that become accessible after neural crest migration are co-enriched for Sox9 and Fox transcription factor binding motifs. In zebrafish lacking Foxc1 paralogs, we find a global decrease in chromatin accessibility in chondrocytes, consistent with a later loss of dorsal facial cartilages. Zebrafish transgenesis assays confirm that many of these Foxc1-dependent elements function as enhancers with region- and stage-specific activity in facial cartilages. These results show that Foxc1 promotes chondrogenesis in the face by establishing chromatin accessibility at a number of cartilage-associated gene enhancers.

Data availability

Chromatin accessibility data have been deposited in GEO under accession number GSE157575.

The following data sets were generated

Article and author information

Author details

  1. Pengfei Xu

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Haoze V Yu

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kuo-Chang Tseng

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4870-7801
  4. Mackenzie Flath

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Peter Fabian

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Neil Segil

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0441-2067
  7. J Gage Crump

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    For correspondence
    gcrump@usc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3209-0026

Funding

National Institute of Dental and Craniofacial Research (R35 DE027550)

  • J Gage Crump

National Institute on Deafness and Other Communication Disorders (R01DC015829)

  • Neil Segil

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (#20771) of the University of Southern California.

Copyright

© 2021, Xu 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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  1. Pengfei Xu
  2. Haoze V Yu
  3. Kuo-Chang Tseng
  4. Mackenzie Flath
  5. Peter Fabian
  6. Neil Segil
  7. J Gage Crump
(2021)
Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation
eLife 10:e63595.
https://doi.org/10.7554/eLife.63595

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https://doi.org/10.7554/eLife.63595