Journal of Biological Chemistry
Volume 279, Issue 45, 5 November 2004, Pages 46818-46825
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Genes: Structure and Regulation
Chromatin-level Regulation of the IL10 Gene in T Cells*

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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 naïve and differentiated murine T cells. Naïve 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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*

This work was supported by National Institutes of Health Grants R01-CA42471 and R01-AI48213 and a grant from the Sandler Program for Asthma Research (to A. R). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Dept. of Internal Medicine III and Inst. for Clinical Immunology and Rheumatology, Friedrich-Alexander-University of Erlangen-Nuremberg, 91054 Erlangen, Germany. Supported by Deutsche Forschungsgemeinschaft Training Grant 592.

**

Supported by a Lady Tata memorial trust fellowship.