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.

中文翻译：

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Foxc1建立颅面软骨分化的增强剂可及性

软骨的规格要求Sox9，这是一种在骨骼系统外器官发生中具有广泛作用的转录因子。尚不清楚在骨骼发育过程中Sox9如何选择性进入软骨特异的顺式调控区域。通过分析神经波峰细胞分化为斑马鱼头的软骨细胞过程中的染色质可及性，我们发现软骨相关的染色质可及性是动态建立的。神经c迁移后可进入的软骨相关区域共富集了Sox9和Fox转录因子结合基序。在缺乏Foxc1旁系同源物的斑马鱼中，我们发现软骨细胞中染色质可及性的总体下降，与后来的背侧软骨丧失一致。斑马鱼转基因测定证实，这些Foxc1依赖性元件中的许多元件都具有增强面部软骨区域和阶段特异性活性的功能。我们建议Foxc1依赖的染色质可访问性有助于将多功能的Sox9蛋白引导到脸上的软骨生成程序。