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Cited by 37Genomics and Chromatin DynamicsOsteoarthritis Treatment and MechanismsConnective tissue disorders research

The dimerization domain of SOX9 is required for transcription activation of a chondrocyte-specific chromatin DNA template

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Coustry, F., Oh, C.-d., Hattori, T., Maity, S. N., de Crombrugghe, B., Yasuda, H.·2010·Nucleic Acids Research
DOI 10.1093/nar/gkq417PMC PMC2952863
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Abstract

Mutations in SOX9, a gene essential for chondrocyte differentiation cause the human disease campomelic dysplasia (CD). To understand how SOX9 activates transcription, we characterized the DNA binding and cell-free transcription ability of wild-type SOX9 and a dimerization domain SOX9 mutant. Whereas formation of monomeric mutant SOX9-DNA complex increased linearly with increasing SOX9 concentrations, formation of a wild-type SOX9-DNA dimeric complex increased more slowly suggesting a more sigmoidal-type progression. Stability of SOX9-DNA complexes, however, was unaffected by the dimerization mutation. Both wild-type and mutant SOX9 activated transcription of a naked Col2a1 DNA template. However, after nucleosomal assembly, only wild-type and not the mutant was able to remodel chromatin and activate transcription of this template. Using a cell line, in which the Col2a1 vector was stably integrated, no differences were seen in the interactions of wild-type and mutant SOX9 with the chromatin of the Col2a1 vector using ChIP. However, the mutant was unable to activate transcription in agreement with in vitro results. We hypothesize that the SOX9 dimerization domain is necessary to remodel the Col2a1 chromatin in order to allow transcription to take place. These results further clarify the mechanism that accounts for CD in patients harboring SOX9 dimerization domain mutations.

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  • SOX9 chromatin binding was unaffected by disrupted dimerization.

    “Interestingly, the same study also showed that SOX9 chromatin binding was unaffected by disrupted dimerization, which is in line with our observation that the monomer motif was more enriched in regions where SOX9 bound but did not open chromatin.”

    From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [18]

    The Results section, “Binding of recombinant full-length and mutant SOX9 to the Col2a1 enhancer” (page unavailable), reports that the dimerization mutant still bound an isolated DNA probe and had similar binding kinetics to wild-type SOX9. The Discussion specifies that this stable binding was to naked DNA; the paper does not establish that binding to chromatin was unaffected. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • A CD mutation affecting SOX9 dimerization impairs chromatin remodeling and transcriptional activation by SOX9.

    “In the same study, a CD mutation which affects SOX9 dimerization was shown to impair chromatin remodeling and transcriptional activation by SOX9.”

    From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [18]

  • SOX9 remodeled chromatin and activated transcription at the COL2A1 enhancer on an in vitro assembled chromatin template.

    “SOX9 remodeled chromatin and activated transcription at this site on an in vitro assembled chromatin template (18).”

    From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [18]

  • Disturbing SOX9 dimerization abolishes its ability to remodel chromatin in vitro.

    “previous study showing that disturbing SOX9 dimerization abolish its ability to remodel chromatin in vitro (18).”

    From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [18]

  • SOX9 must dimerize to open chromatin.

    “Our results strongly suggests that SOX9 must dimerize to open chromatin in agreement with the previous study showing that disturbing SOX9 dimerization abolish its ability to remodel chromatin in vitro (18).”

    From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [18]

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Research works printed but not linked: 28

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Authors
Coustry, F., Oh, C.-D., Hattori, T., Maity, S. N., de Crombrugghe, B., & Yasuda, H.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Yasuda, H.
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2010-05-19
Volume
38
Issue
18
Pages
6018-6028
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkq417
PMC
PMC2952863
OpenAlex
W2164202117
Cited by
37
References
1
Citations by year
2026: 1 · 2022: 7 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 2 · 2012: 4
FWCI
0.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Arthritis Foundation
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 042919, AR053568, P01AR042919, R01AR053568)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
Keywords
SOX9, dimerization domain, transcriptional activation, chondrogenic differentiation, campomelic dysplasia, COL2A1, chromatin remodeling, nucleosome assembly, transcription factor mutations
MeSH terms
Animals, Cell Line, Chromatin, DNA, Enhancer Elements, Genetic, Humans, Mutation, Recombinant Proteins, Transcriptional Activation, Protein Structure, Tertiary, Dimerization, Chondrocytes, Collagen Type II, Chromatin Assembly and Disassembly, SOX9 Transcription Factor

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