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Identification of a Macrophage-Specific Chromatin Signature in the IL-10 Locus
- Source :
- The Journal of Immunology. 175:1041-1046
- Publication Year :
- 2005
- Publisher :
- The American Association of Immunologists, 2005.
-
Abstract
- The molecular mechanisms that regulate expression of the immunosuppressive cytokine IL-10 remain poorly understood. In this study, by measuring sensitivity to DNase I digestion, we show that production of IL-10 by primary mouse bone marrow-derived macrophages stimulated through pattern recognition receptors was associated with chromatin remodeling of the IL-10 locus. We also demonstrate that the IL-10 locus is remodeled in primary Th2 cells and IL-10-producing regulatory T cells that have been differentiated in vitro. Strikingly, a novel DNase I-hypersensitive site (HSS-4.5) was identified in stimulated macrophages, but not in T cells. We show that hyperacetylated histones were recruited to this site in stimulated macrophages. Furthermore, HSS-4.5 is highly conserved and contains a putative NF-κB binding site. In support of a function for this site, NF-κB p65/RelA was recruited to HSS-4.5 in vivo and its activation was required for optimal IL-10 gene expression in LPS-stimulated macrophages.
- Subjects :
- Genetic Markers
Lipopolysaccharides
medicine.medical_treatment
Molecular Sequence Data
Immunology
Bone Marrow Cells
Regulatory Sequences, Nucleic Acid
Resting Phase, Cell Cycle
T-Lymphocytes, Regulatory
Chromatin remodeling
Mice
Th2 Cells
medicine
Animals
Deoxyribonuclease I
Humans
Immunology and Allergy
Binding site
Mice, Inbred BALB C
Base Sequence
biology
Macrophages
NF-kappa B
Transcription Factor RelA
Cell Differentiation
Dendritic Cells
Macrophage Activation
Molecular biology
Chromatin
Interleukin-10
Protein Transport
Interleukin 10
Histone
Cytokine
Regulatory sequence
biology.protein
DNase I hypersensitive site
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 175
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....421084a90c670fd9100441b9b46c0412