Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation
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- Pengfei Xu
- Eli and Edythe Broad Center for Regenerative Medicine, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States
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- Haoze V Yu
- Eli and Edythe Broad Center for Regenerative Medicine, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States
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- Kuo-Chang Tseng
- Eli and Edythe Broad Center for Regenerative Medicine, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States
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- Mackenzie Flath
- Eli and Edythe Broad Center for Regenerative Medicine, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States
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- Peter Fabian
- Eli and Edythe Broad Center for Regenerative Medicine, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States
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- Neil Segil
- Eli and Edythe Broad Center for Regenerative Medicine, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States
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- J Gage Crump
- Eli and Edythe Broad Center for Regenerative Medicine, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States
説明
<jats:p>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.</jats:p>
収録刊行物
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- eLife
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eLife 10 e63595-, 2021-01-27
eLife Sciences Publications, Ltd
