Cited by 101Osteoarthritis Treatment and MechanismsGenomics and Chromatin DynamicsProteoglycans and glycosaminoglycans research

SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters

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Oh, Chun-do, Lu, Yue, Liang, Shoudan, Mori-Akiyama, Yuko, Chen, Di, de Crombrugghe, Benoit, Yasuda, Hideyo·2014·PLoS ONE

Abstract

The transcription factor SOX9 plays an essential role in determining the fate of several cell types and is a master factor in regulation of chondrocyte development. Our aim was to determine which genes in the genome of chondrocytes are either directly or indirectly controlled by SOX9. We used RNA-Seq to identify genes whose expression levels were affected by SOX9 and used SOX9 ChIP-Seq to identify those genes that harbor SOX9-interaction sites. For RNA-Seq, the RNA expression profile of primary Sox9flox/flox mouse chondrocytes infected with Ad-CMV-Cre was compared with that of the same cells infected with a control adenovirus. Analysis of RNA-Seq data indicated that, when the levels of Sox9 mRNA were decreased more than 8-fold by infection with Ad-CMV-Cre, 196 genes showed a decrease in expression of at least 4-fold. These included many cartilage extracellular matrix (ECM) genes and a number of genes for ECM modification enzymes (transferases), membrane receptors, transporters, and others. In ChIP-Seq, 75% of the SOX9-interaction sites had a canonical inverted repeat motif within 100 bp of the top of the peak. SOX9-interaction sites were found in 55% of the genes whose expression was decreased more than 8-fold in SOX9-depleted cells and in somewhat fewer of the genes whose expression was reduced more than 4-fold, suggesting that these are direct targets of SOX9. The combination of RNA-Seq and ChIP-Seq has provided a fuller understanding of the SOX9-controlled genetic program of chondrocytes.

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Crossref · 10.1371/journal.pone.0107577

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  • Among upregulated genes were previously characterized SOX9 target genes, such as ECM genes encoding collagens IX and XI, as well as TF genes SOX5, SOX6, CREB3L2, and NFIA.

    “Among the upregulated genes were previously characterized SOX9 target genes, such as ECM genes encoding collagens IX and XI (53), as well as other TF genes like SOX5, SOX6, CREB3L2, and NFIA”
  • The identified SOX motifs are similar to previously identified motifs for SOX9.

    “which are similar to previously identified motifs for SOX9 (5,17,53,62).”

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Authors
Oh, C.-D., Lu, Y., Liang, S., Mori-Akiyama, Y., Chen, D., de Crombrugghe, B., & Yasuda, H.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Rush University Medical Center (US)
Corresponding author
Yasuda, Hideyo
Venue
PLoS ONE
Published
2014-09-17
Volume
9
Issue
9
Pages
e107577
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2040278668
Cited by
101
References
54
Citations by year
2026: 2 · 2025: 6 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 17 · 2019: 10 · 2018: 6 · 2017: 6 · 2016: 11 · 2015: 14
FWCI
8.59
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Institutes of Health (CA-16 672)
  • University of Texas MD Anderson Cancer Center (#CA16672)
  • National Cancer Institute (CA-16672, P30CA016672)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR309854, R01AR054465)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Keywords
SOX9, chondrocytes, transcriptional regulation, extracellular matrix genes, transcription factor binding sites, gene expression profiling, Cre-loxP conditional knockout, chondrogenesis, cell surface receptors, transporters
MeSH terms
Animals, Binding Sites, Gene Expression Regulation, Humans, Protein Binding, Gene Expression, Extracellular Matrix Proteins, Mice, Knockout, Chondrocytes, Gene Expression Profiling, Protein Transport, Chromatin Immunoprecipitation, Mice, SOX9 Transcription Factor, Position-Specific Scoring Matrices, High-Throughput Nucleotide Sequencing, Nucleotide Motifs

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