Researchers at the University of Tokyo now understand more about the mechanisms behind cartilage formation by using big data to unpack the action of the Sox9 protein during cartilage formation. The research was published in Cell Reports.
Cartilage formation is important in skeletal growth until puberty, and in the articulation of joints. The process of chondrogenesis is regulated by expression of the protein Sox9, encoded by the gene SOX9. Mutations in the SOX9 gene cause campomelic dysplasia, a which leads to skeletal abnormalities and disorders of the reproductive system.
The team used big data techniques to analyse information on Sox9 location, chromatin state, and gene expression over the whole mouse genome. They identified two genome-wide modes (Class I and Class II engagement) of Sox9 action in transcription during chondrogenesis. In Class I engagement, Sox9 binds indirectly to the DNA and regulates the transcription of genes involved in basal cell activities. In Class II engagement, it binds directly to the DNA in multiple locations and activates transcription of cartilage-related genes.
“This finding will contribute to the understanding of cartilage-related degenerative diseases and congenital abnormalities that are caused by genomic mutation and genome-based drug discovery for treatment of diseases and cartilage regeneration,” says Shinsuke Ohba of the Department of Bioengineering.