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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2009-1-26
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pubmed:abstractText |
IL-10 is a multifunctional cytokine that plays a critical role in maintaining the balance between immunity and tolerance. Previously, we identified proximal regulatory elements and alterations of chromatin structure in the IL-10 gene loci of Th1 and Th2 cells. We have now characterized a crucial cis-regulatory element, CNS-9, located 9kb upstream of the transcription start site in IL-10 gene loci. The CNS-9 region is highly conserved in vertebrate genomes, and contains clustered NFAT and IRF binding motifs. In vitro binding of NFAT1 and IRF4 to the CNS-9 region was observed by EMSA. Furthermore, Th2-preferential in vivo binding of NFAT1 and IRF4 to the CNS-9 region was observed by ChIP. Cyclosporine A treatment on wild type Th2 cells or Th2 cells derived from NFAT1 knockout (NFAT1(-/-)) mice showed significantly reduced trans-activity of CNS-9. The Th2 subset-specific enhancer activity of CNS-9 was upregulated synergistically by NFAT1 and its partner IRF4. Mutations in the binding sites for NFAT1 and IRF4 abrogated its enhancer activity of CNS-9. Collectively, our results establish crucial roles for enhancer element CNS-9, and NFAT1 and IRF4 that bind to it, for IL-10 expression in differential T helper subsets.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0161-5890
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pubmed:author |
pubmed-author:HwangKi-ChulKC,
pubmed-author:ImSin-HyeogSH,
pubmed-author:KangKyu-HoKH,
pubmed-author:KwonHo-KeunHK,
pubmed-author:LeeChoong-GuCG,
pubmed-author:MatsuyamaToshifumiT,
pubmed-author:SahooAnupamaA,
pubmed-author:SoJae-SeonJS,
pubmed-author:SonJun-SeockJS,
pubmed-author:SongMin-KyungMK,
pubmed-author:YiHwa-JoongHJ,
pubmed-author:YuiKatsuyukiK
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pubmed:issnType |
Print
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pubmed:volume |
46
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
613-21
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pubmed:meshHeading |
pubmed-meshheading:18962896-Animals,
pubmed-meshheading:18962896-Cell Line, Tumor,
pubmed-meshheading:18962896-Cyclosporine,
pubmed-meshheading:18962896-Enhancer Elements, Genetic,
pubmed-meshheading:18962896-Humans,
pubmed-meshheading:18962896-Interferon Regulatory Factors,
pubmed-meshheading:18962896-Interleukin-10,
pubmed-meshheading:18962896-Mice,
pubmed-meshheading:18962896-Mice, Inbred C57BL,
pubmed-meshheading:18962896-Mice, Knockout,
pubmed-meshheading:18962896-NFATC Transcription Factors,
pubmed-meshheading:18962896-Signal Transduction,
pubmed-meshheading:18962896-Th1 Cells,
pubmed-meshheading:18962896-Th2 Cells,
pubmed-meshheading:18962896-Transcriptional Activation
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pubmed:year |
2009
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pubmed:articleTitle |
A distal cis-regulatory element, CNS-9, controls NFAT1 and IRF4-mediated IL-10 gene activation in T helper cells.
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pubmed:affiliation |
Department of Life Sciences, Gwangju Institute of Science and Technology (GIST), 1 Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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