ArticleMolecular and cellular biology2008
L-Sox5 and Sox6 drive expression of the aggrecan gene in cartilage by securing binding of Sox9 to a far-upstream enhancer.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers.
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Who cites it
170 citing papers in PubMed, 296 citations in OpenAlex.
- Regulation of human chondrocyte function through direct inhibition of cartilage master regulator SOX9 by microRNA-145 (miRNA-145).The Journal of biological chemistry · 2012Trial
- CRISPR activation reveals SOX5/6/9 as key transcriptional regulators directing iPSC-derived cells toward a notochordal lineage.Stem cell reports · 2026Article
- Single-cell multi-omics defines H3K27me3 remodelling in intervertebral disc degeneration with implications for regenerative intervention.Bone research · 2026Article
- SOX6 is expressed in various cell lineages in the developing mouse heart and contributes to proper valvuloseptal development.Anatomical record (Hoboken, N.J. : 2007) · 2026Article
- Understanding the use of spheroids and pellets in the chondrogenic differentiation of human stem cells.Osteoarthritis and cartilage open · 2026Article
- A Campomelic Dysplasia A76E Mutation in Sox9 Destabilizes Protein and DNA Binding Dynamics.Biomolecules · 2026Article
- Stage- and cluster-specific regulation of chondrogenic gene programs by Sox9 in mouse embryonic limb buds.iScience · 2026Article
- Discovery ofDiagnostics (Basel, Switzerland) · 2025Article
- Sox9 in the second heart field and the development of the outflow tract; implications for cardiac septation and valve formation.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Evolutionary trends in the emergence of skeletal cell types.Evolution letters · 2025Article
- Blocking calcium-MYC regulatory axis inhibits early dedifferentiation of chondrocytes and contributes to cartilage regeneration.Stem cell research & therapy · 2025Article
- Functional characterization of SOX5 variant causing Lamb-Shaffer syndrome and literature review of variants in the SOX5 gene.Orphanet journal of rare diseases · 2025Review
- The Expression Level of SOX Family Transcription Factors' mRNA as a Diagnostic Marker for Osteoarthritis.Journal of clinical medicine · 2025Article
- Fgfr3 enhancer deletion markedly improves all skeletal features in a mouse model of achondroplasia.The Journal of clinical investigation · 2025Article
- Sustained Delivery of Chondrogenic Molecules Using Sugar Glass Nanoparticle-Integrated Fibrous Scaffolds for Cartilage Tissue Engineering.Regenerative engineering and translational medicine · 2025Article
- Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes.Journal of cellular physiology · 2025Article
- MLL4 regulates postnatal palate growth and midpalatal suture development.Frontiers in cell and developmental biology · 2025Article
- Voluntary exercise in mice triggers an anti-osteogenic and pro-tenogenic response in the ankle joint without affecting long bones.Bone reports · 2024Article
- SOX-5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women.ACR open rheumatology · 2024Article
- Engineering gene-activated bioprinted scaffolds for enhancing articular cartilage repair.Materials today. Bio · 2024Review
110 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Sry-related high-mobility-group box transcription factor Sox9 recruits the redundant L-Sox5 and Sox6 proteins to effect chondrogenesis, but the mode of action of the trio remains unclear. We identify here a highly conserved 359-bp sequence 10 kb upstream of the Agc1 gene for aggrecan, a most essential cartilage proteoglycan and key marker of chondrocyte differentiation. This sequence directs expression of a minimal promoter in both embryonic and adult cartilage in transgenic mice, in a manner that matches Agc1 expression. The chondrogenic trio is required and sufficient to mediate the activity of this enhancer. It acts directly, Sox9 binding to a critical cis-acting element and L-Sox5/Sox6 binding to three additional elements, which are cooperatively needed. Upon binding to their specific sites, L-Sox5/Sox6 increases the efficiency of Sox9 binding to its own recognition site and thereby robustly potentiates the ability of Sox9 to activate the enhancer. L-Sox5/Sox6 similarly secures Sox9 binding to Col2a1 (encoding collagen-2) and other cartilage-specific enhancers. This study thus uncovers critical cis-acting elements and transcription factors driving Agc1 expression in cartilage and increases understanding of the mode of action of the chondrogenic Sox trio.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.