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.
Lefebvre
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V
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
Li
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P
de Crombrugghe
B
B
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