Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation [article]

Pengfei Xu, Haoze V Yu, Kuo-Chang Tseng, Mackenzie Flath, Peter Fabian, Neil Segil, J Gage Crump
2020 bioRxiv   pre-print
The specification of cartilage requires Sox9, a transcription factor with broad roles for organogenesis outside the skeletal system. How Sox9 gains selective access to cartilage specific cis-regulatory regions during skeletal development had remained unclear. 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
more » ... s 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. We propose that Foxc1-dependent chromatin accessibility helps directs the versatile Sox9 protein to a chondrogenic program in the face.
doi:10.1101/2020.10.15.340703 fatcat:7ochndr4fba2rgv27khkf6xp2u