IL-10 Gene Expression Is Controlled by the Transcription Factors Sp1 and Sp3
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IL-10 is an 18-kDa cytokine with a key role in homeostatic control of inflammatory and immune responses. We have investigated how transcription of the IL-10 gene is regulated, so as to be able to understand the circumstances of IL-10 expression in both health and disease. In the mouse, IL-10 gene expression is regulated by a TATA-type promoter with a critical cis-acting element containing GGA repeats located at −89 to −77. Its complementary sequence is similar to the cis-acting elements (TCC repeats) in the promoters of genes encoding epidermal growth factor receptor and CD58. All these elements comprise a common CCTCCT sequence with less conserved C + T-rich sequences. Eliminating this CCTCCT sequence results in a marked reduction in promoter activity, suggesting a necessary role in IL-10 gene expression. Despite its dissimilarity to the G + C-rich Sp1 consensus sequence (GC box), Sp1 and Sp3 transcription factors could be shown to bind to this motif. The requirement for Sp1 and Sp3 in transcription of IL-10 was confirmed using Drosophila SL2 cells, which lack endogenous Sp factors. These results suggest that the transcription of IL-10 is positively regulated by both Sp1 and Sp3.
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Sp1 and STAT3 are transcription factors known to interact with the Il10 promoter.
“transcription factors known to interact with the Il10 promoter25,26.”
From The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance (2009) · cites this paper as [26]
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References 42 · Cited by 250
- Authors
- Tone, M., Powell, M. J., Tone, Y., Thompson, S. A. J., & Waldmann, H.
- Affiliations
- University of Oxford (GB)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-07-01
- Volume
- 165
- Issue
- 1
- Pages
- 286-291
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1817548159
- Cited by
- 250
- References
- 42
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 8 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 10 · 2015: 9 · 2014: 14 · 2013: 11 · 2012: 9
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-10, transcriptional regulation, Sp1, Sp3, promoter cis-acting elements, TATA box, Sp1 binding site, cytokine expression
- MeSH terms
- Animals, Base Sequence, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding, Regulatory Sequences, Nucleic Acid, Transcription Factors, Sp1 Transcription Factor, Interleukin-10, 5' Untranslated Regions, Mice, Sp3 Transcription Factor
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