SOX9 Is a Potent Activator of the Chondrocyte-Specific Enhancer of the Proα1(II) Collagen Gene

• DOI: 10.1128/mcb.17.4.2336
• Publication Date: 2015-10-09T22:07:21Z
• Authors: Véronique Lefebvre; Wendong Huang; Vincent R. Harley; Peter N. Goodfellow; Benoit de Crombru...
• Keywords: SOX9; Enhancer RNAs

The identification of mutations in the SRY-related SOX9 gene patients with campomelic dysplasia, a severe skeletal malformation syndrome, and abundant expression Sox9 mouse chondroprogenitor cells fully differentiated chondrocytes during embryonic development have suggested hypothesis that might play role chondrogenesis. Our previous experiments (Col2a1) for collagen II, an early marker chondrocyte differentiation, identified minimal DNA element intron 1 which directs chondrocyte-specific transgenic mice. This is also strong enhancer transient transfection experiments. We show here Col2a1 closely correlated high levels RNA protein chondrocytes. indicate direct target Sox9. Indeed, binds to sequence essential activity chondrocytes, acts as potent activator this cotransfection nonchondrocytic cells. Mutations prevent binding abolish suppress activation by Other SOX family members are ineffective. Expression truncated lacking transactivation domain but retaining DNA-binding interferes full-length fibroblasts inhibits results strongly suggest model whereby involved control cell-specific COL2A1 component differentiation program these speculate dysplasia decrease would inhibit production eventually other cartilage matrix proteins, leading major anomalies.