Sox9
Sox9 (SRY-box transcription factor 9, also known as SRA1, CMD1 and CMPD1) is a nuclear HMG-box transcription factor that directs chondrocyte differentiation and skeletal development. It also regulates proliferation and differentiation in epithelial stem and progenitor cells. Browse Assay Genie's current range of Sox9 research reagents below, or read on for the biology behind the target.
Sox9 is a transcription factor that binds the 5'-ACAAAG-3' DNA motif found in enhancers and super-enhancers, and also binds some promoter regions. Through these sites it promotes expression of genes important for chondrogenesis, including the cartilage matrix genes COL2A1, COL4A2, COL9A1, COL11A2 and ACAN, as well as SOX5 and SOX6. It helps, but is not required, to remove epigenetic marks of repression and to deposit active promoter and enhancer marks at chondrocyte-specific genes. It acts in cooperation with the Hedgehog-dependent GLI1 and GLI3 transcription factors.
The protein acts at successive steps of chondrocyte differentiation. It is absolutely required for precartilaginous condensation, when skeletal progenitors become prechondrocytes. Together with SOX5 and SOX6 it is needed for overt chondrogenesis, when condensed prechondrocytes become early chondrocytes. Later, in growth plate chondrocytes, it maintains columnar proliferation, delays prehypertrophy and blocks osteoblast differentiation by lowering beta-catenin (CTNNB1) signalling and RUNX2 expression. It also supports hypertrophy by preserving chondrocyte lineage fate and by transactivating COL10A1 with MEF2C. Under low lipid conditions, FOXO1 and FOXO3 promote Sox9 expression, which drives chondrogenic commitment and suppresses fatty acid oxidation.
Beyond cartilage, Sox9 regulates epithelial stem and progenitor cells. In the lung it balances proliferation and differentiation during branching morphogenesis and regulates the extracellular matrix, and it controls epithelial branching in kidney development. NCBI Gene notes that it recognises the sequence CCTTGAG like other HMG-box DNA-binding proteins and, with steroidogenic factor 1, regulates transcription of the anti-Muellerian hormone (AMH) gene. Deficiencies cause campomelic dysplasia, a skeletal malformation syndrome frequently accompanied by sex reversal, which explains the previous gene name. The Sox9 gene has mouse and rat orthologs with the same symbol.
Sox9 is required for precartilaginous condensation and drives cartilage matrix genes such as COL2A1 and ACAN, making it a central marker of chondrocyte differentiation.
Sox9 delays prehypertrophy and blocks osteoblast differentiation by lowering beta-catenin signalling and RUNX2 expression, shaping growth plate maturation.
Sox9 balances proliferation and differentiation in lung epithelium and controls epithelial branching in kidney development.
Sox9 regulates AMH transcription with steroidogenic factor 1, and its deficiency causes campomelic dysplasia, often with sex reversal.
Sox9 is a nuclear transcription factor that binds the 5'-ACAAAG-3' motif and drives chondrocyte differentiation and skeletal development. It is required for precartilaginous condensation and, with SOX5 and SOX6, for overt chondrogenesis. It also regulates epithelial progenitors in the lung and kidney.
The HGNC name is SRY-box transcription factor 9, and UniProt calls the protein transcription factor SOX-9. Aliases and previous symbols include SRA1, CMD1 and CMPD1. Earlier names were campomelic dysplasia, autosomal sex-reversal, and SRY (sex determining region Y)-box 9.
Deficiencies in the Sox9 gene lead to campomelic dysplasia, a skeletal malformation syndrome frequently with sex reversal. Mouse and rat both have a Sox9 ortholog, so rodent models are used to study it. Check the datasheet of any product for its validated reactivity.
Other SRY-box transcription factors, including the SOX5 and SOX6 partners of Sox9 in chondrogenesis, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P48436; product specifications from Assay Genie datasheets.