Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation

• Main Authors: Pengfei Xu, Haoze V Yu, Kuo-Chang Tseng, Mackenzie Flath, Peter Fabian, Neil Segil, J Gage Crump
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2021-01-01
• Series: eLife
• Subjects: cartilage; craniofacial; cranial neural crest; Foxc1; Sox9; epigenetics
• Online Access: https://elifesciences.org/articles/63595

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.