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bioRxiv · 10.1101/2020.10.15.340703

Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation

Xu, P.·Yu, H. V.·Tseng, K.-C.·Flath, M.·Fabian, P.·Segil, N.·Crump, J. G.
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Abstract

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 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. We propose that Foxc1-dependent chromatin accessibility helps directs the versatile Sox9 protein to a chondrogenic program in the face. HighlightsO_LIDynamic chromatin accessibility across facial cartilage development C_LIO_LICo-enrichment of Fox- and Sox-binding motifs in accessible regions C_LIO_LIFoxc1 establishes accessibility in a subset of facial cartilage enhancers C_LIO_LIModular activity of Foxc1-dependent cartilage enhancers in zebrafish C_LI

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Xu, P., Yu, H. V., Tseng, K.-C., Flath, M., Fabian, P., Segil, N., Crump, J. G.. 2020-10-15. Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation. https://doi.org/10.1101/2020.10.15.340703

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