“Identification of Critical Genome Regions and their Regulatory Mechanisms in Chondrocytes: Expectations for Understanding the Pathogenic Mechanisms of Cartilage Genetic Diseases”

Department Molecular and Cellular Biochemistry

A research group has discovered genome regions that control the expression of the Sox9 gene in chondrocytes, shedding light on their importance in skeletal development.

The SOX9 gene is an essential transcription factor for chondrocyte differentiation. Mutations in and around the SOX9 gene can cause inherited bone and cartilage disorders such as campomelic dysplasia and Pierre Robin syndrome.

To promote the transcription followed by the gene expression, a genomic region called the “enhancer” is critical. Until now, the enhancer(s) for SOX9 gene expression in chondrocyte differentiation and skeletal development remains to be elucidated.

In this study, the research group utilized next-generation sequencing analysis and genome editing technology to reveal the critical enhancers and their regulatory mechanisms for Sox9 gene expression in chondrocytes. The enhancers were found to exist at genomic distances of 160kb and 308kb away from the Sox9 gene, synergistically controlling chondrocyte differentiation and skeletal development.

This discovery would contribute to the better understanding of the pathogenic mechanisms underlying cartilage genetic diseases caused by the SOX9 gene.

This article, “Chromatin profiling identifies chondrocyte-specific Sox9 enhancers
important for skeletal development” was published in JCI Insight at DOI: