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Cited by 811Osteoarthritis Treatment and MechanismsDevelopmental Biology and Gene RegulationGenomics and Chromatin Dynamics

A new long form of Sox5 (L‐Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene

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Lefebvre, Véronique, Li, Ping, de Crombrugghe, Benoit·1998·The EMBO Journal
DOI 10.1093/emboj/17.19.5718PMC PMC1170900
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Abstract

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.

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  • Few studies have conclusively shown that TF multimerisation is a pre-requisite for efficient DNA-binding, but more recent works on BTB domain proteins and FOXP3 have suggested that higher-order assemblies of these TFs are needed for their cellular functions.

    “Few studies have conclusively shown that TF multimerisation is a pre-requisite for efficient DNA-binding (e.g. SOX6 73 ), but more recent works on BTB domain proteins 74 and FOXP3 75 have suggested that higher-order assemblies of these TFs are needed for their cellular functions.”

    From Tetramerisation governs SALL transcription factor function in development and disease (2025) · cites this paper as [73]

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Cited by

Sorted by citations

Authors
Lefebvre, V., Li, P., & de Crombrugghe, B.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
1998-10-01
Volume
17
Issue
19
Pages
5718-5733
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.1093/emboj/17.19.5718
PMC
PMC1170900
OpenAlex
W2102047286
Cited by
811
References
0
Citations by year
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FWCI
18.00
Type
journal article
Language
en
Open access
Licence
Locations
  • The EMBO Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1r01ar042909-01)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (P01AR042919, R01 AR42909, P01 AR42919-12)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
SOX5, SOX6, SOX9, chondrogenesis, type II collagen, COL2A1, HMG-box transcription factor, coiled-coil domain, protein dimerization, enhancer activation, chondrogenic differentiation, transcriptional cooperation, mouse embryo
MeSH terms
Amino Acid Sequence, Animals, Cartilage, Cell Differentiation, Collagen, DNA-Binding Proteins, Enhancer Elements, Genetic, High Mobility Group Proteins, Molecular Sequence Data, Nuclear Proteins, Protein Binding, RNA, Messenger, Transcription Factors, Sequence Homology, Amino Acid, Protein Structure, Secondary, DNA, Complementary, Gene Expression Regulation, Developmental, Dimerization, Chondrogenesis, Mice, SOXD Transcription Factors, SOX9 Transcription Factor

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