Cited by 103Genomics and Chromatin DynamicsT-cell and B-cell ImmunologyEpigenetics and DNA Methylation

Chromatin-level Regulation of the IL10 Gene in T Cells

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Im, Sin-Hyeog, Hueber, Axel, Monticelli, Silvia, Kang, Kyu-Ho, Rao, Anjana·2004·Journal of Biological Chemistry

Abstract

The immunoregulatory cytokine interleukin 10 (IL-10) modulates the function of diverse immune and non-immune cells. Here, we examine the chromatin structural changes associated with IL10 gene transcription by naive and differentiated murine T cells. Naive T cells lack DNase I hypersensitive (HS) sites in the vicinity of the IL10 gene, whereas differentiated T cells display a strong 3' constitutive HS site as well as several inducible sites. The majority of HS sites map to regions that are strongly conserved in sequence between mouse and human genomes. In committed Th1 cells, the mechanism of IL10 gene silencing is associated with the development of repressive histone modifications near the IL10 promoter and also near intronic hypersensitive regions of the IL10 gene. Our results constitute the first report of chromatin structural differences within the IL10 gene in differentiated Th1 and Th2 cells and emphasize the surprising diversity of mechanisms used to regulate cytokine gene expression at the chromatin level.

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Crossref · 10.1074/jbc.m401722200

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Authors
Im, S.-H., Hueber, A., Monticelli, S., Kang, K.-H., & Rao, A.
Affiliations
  • Gwangju Institute of Science and Technology (KR)
  • Harvard University (US)
Corresponding author
Im, Sin-Hyeog
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-11
Volume
279
Issue
45
Pages
46818-46825
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2021626420
Cited by
103
References
24
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 1 · 2016: 6 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 8
FWCI
2.60
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (R01CA042471, R01 CA-42471)
  • National Institute of Allergy and Infectious Diseases (R01 AI 48213, R01AI048213)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
IL-10, IL-10 gene, chromatin structure, DNase I hypersensitive sites, T cells, Th1 cells, Th2 cells, histone modifications, gene silencing, cytokine gene expression, naive T cells, promoter repression
MeSH terms
Animals, Base Sequence, Binding Sites, Cell Differentiation, Chromatin, Deoxyribonuclease I, DNA, Gene Expression Regulation, Introns, Mice, Transgenic, Models, Genetic, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding, T-Lymphocytes, Transcription, Genetic, Cytokines, Interleukin-10, DNA Primers, Th1 Cells, Th2 Cells, DNA Methylation, Physical Chromosome Mapping, Gene Silencing, Chromatin Immunoprecipitation, Immunoprecipitation, Mice

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