Medicine and Health Sciences Commons^™

The Sox9 Upstream Region Prone To Chromosomal Aberrations Causing Campomelic Dysplasia Contains Multiple Cartilage Enhancers, Baojin Yao, Qiuqing Wang, Chia-Feng Liu, Pallavi Bhattaram, Wei Li, Timothy J. Mead, James F. Crish, Véronique Lefebvre

Biomedical Sciences

Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized skeleton malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –350/–50-kb region 5 of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at – 250 kb) confines its activity to condensed prechondrocytes, …