Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation
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.
Chromatin accessibility data have been deposited in GEO under accession number GSE157575.
Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiationNCBI Gene Expression Omnibus, GSE157575.
Article and author information
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.
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.
- Carole LaBonne, Northwestern University, United States
- Received: September 29, 2020
- Accepted: January 26, 2021
- Accepted Manuscript published: January 27, 2021 (version 1)
- Version of Record published: February 18, 2021 (version 2)
© 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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