Mouse Transcription Factor SOX 9,SOX9 ELI

Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:10319868, PubMed:11371614, PubMed:12414734, PubMed:15132997, PubMed:18415932, PubMed:20940257, PubMed:28263186).

Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including cartilage matrix protein-coding genes COL2A1, COL4A2, COL9A1, COL11A2 and ACAN, SOX5 and SOX6 (PubMed:9119111, PubMed:10805756, PubMed:12414734, PubMed:15694126, PubMed:17525254, PubMed:26146088, PubMed:26150426, PubMed:26910618, PubMed:28263186).

Also binds to some promoter regions (PubMed:20940257).

Plays a central role in successive steps of chondrocyte differentiation (PubMed:11371614, PubMed:12414734, PubMed:22421045).

Absolutely required for precartilaginous condensation, the first step in chondrogenesis during which skeletal progenitors differentiate into prechondrocytes (PubMed:11371614, PubMed:12414734).

Together with SOX5 and SOX6, required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes, the second step in chondrogenesis (PubMed:11371614, PubMed:12414734, PubMed:15529345).

Later, required to direct hypertrophic maturation and block osteoblast differentiation of growth plate chondrocytes: maintains chondrocyte columnar proliferation, delays prehypertrophy and then prevents osteoblastic differentiation of chondrocytes by lowering beta-catenin (CTNNB1) signaling and RUNX2 expression (PubMed:22421045, PubMed:31121357).

Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells and transactivating COL10A1 along with MEF2C (PubMed:21367821, PubMed:22421045).

Low lipid levels are the main nutritional determinant for chondrogenic commitment of skeletal progenitor cells: when lipids levels are low, FOXO (FOXO1 and FOXO3) transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (PubMed:32103177).

Mechanistically, helps, but is not required, to remove epigenetic signatures of transcriptional repression and deposit active promoter and enhancer marks at chondrocyte-specific genes (PubMed:30021842).

Acts in cooperation with the Hedgehog pathway-dependent GLI (GLI1 and GLI3) transcription factors (PubMed:29659575).

In addition to cartilage development, also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells: involved in the lung epithelium during branching morphogenesis, by balancing proliferation and differentiation and regulating the extracellular matrix (PubMed:24191021).

Controls epithelial branching during kidney development (PubMed:21212101).

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