A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene.
Transcripts for a new form of Sox5, called L-Sox5, and Sox6 are coexpressed with Sox9 in all chondrogenic sites of mouse embryos. A coiled-coil domain located in the N-terminal part of L-Sox5, and absent in Sox5, showed >90% identity with a similar domain in Sox6 and mediated homodimerization and heterodimerization with Sox6. Dimerization of L-Sox5/Sox6 greatly increased efficiency of binding of the two Sox proteins to DNA containing adjacent HMG sites. L-Sox5, Sox6 and Sox9 cooperatively activated expression of the chondrocyte differentiation marker Col2a1 in 10T1/2 and MC615 cells. A 48 bp chondrocyte-specific enhancer in this gene, which contains several HMG-like sites that are necessary for enhancer activity, bound the three Sox proteins and was cooperatively activated by the three Sox proteins in non-chondrogenic cells. Our data suggest that L-Sox5/Sox6 and Sox9, which belong to two different classes of Sox transcription factors, cooperate with each other in expression of Col2a1 and possibly other genes of the chondrocytic program.
Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 11, Houston, TX 77030, USA. veronique_lefebvre@molgen.tmc.edu
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D000595:Amino Acid Sequence; D000818:Animals; D002356:Cartilage / Q000196:embryology; D002454:Cell Differentiation; D020219:Chondrogenesis / Q000235:genetics*; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D019281:Dimerization; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000096:biosynthesis*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics; D055758:SOX9 Transcription Factor; D055755:SOXD Transcription Factors; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000096:biosynthesis*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; D055755:SOXD Transcription Factors; C089186:Sox5 protein, mouse; C095939:Sox6 protein, mouse; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D003094:Collagen