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DNA methylation and not allelic variation regulates STAT6 expression in human T cells

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Abstract

STAT6 transcription factor, which has been implicated in commitment to Th2, is known to be activated by IL-4 and IL-13. Accordingly, STAT6 is primarily responsible for the transcriptional effects of IL-4 and IL-13. STAT6-deficient mice are known to have defective IL-4-mediated functions, such as B cell proliferation, Th2 cell development and IgE secretion; therefore, they primarily contain the Th1 phenotype. However, the mechanism responsible for regulation of STAT6 expression transcriptionally and post-transcriptionally has yet to be elucidated. Here, we characterized the human STAT6 promoter gene and found that the transcriptional regulatory elements CCAAT and ATF were important for the STAT6 promoter activity. Direct sequencing analysis revealed that the 13 GT repeat allelic variation in noncoding exon 1 of the STAT6 gene appeared more frequently in 91 patients with asthma or rheumatoid arthritis than the 15 GT repeat variation, which is the dominant phenotype in healthy controls. However, it appears that this allelic variation did not affect the STAT6 transcriptional activity. Interestingly, treatment with a DNA methyltransferase inhibitor markedly increased the expression of STAT6 mRNA and protein in human primary T cells. In contrast, IFN-γ treatment significantly repressed the STAT6 transcriptional activity. Therefore, the present study provides insight into the molecular basis of STAT6 expression, and in particular, demonstrates that STAT6 expression is associated with DNA hypermethylation rather than promoter polymorphisms or allelic variations.

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Acknowledgments

This work was supported by the Korea Science and Engineering Foundation (KOSEF) [R01-2007-000-20007-0, 2008)] and KOSEF through the Rheumatism Research Center (R11-2002-098-05003, 2008) grants funded by the Korea government.

Conflict of interest statement

The authors declare that they have no conflict of interest related to the publication of this manuscript.

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Authors and Affiliations

  1. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi, 440-746, Korea

    Eu-Gene Kim, Hyun-Jin Shin, Chang Geun Lee, Hye-Young Park & Chang-Woo Lee

  2. Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi, 440-746, Korea

    Hyun-Jin Shin, Chang Geun Lee & Chang-Woo Lee

  3. Department of Life Science, Pohang University of Science and Technology, Pohang, 790-784, Korea

    Yoon-Keun Kim

  4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea

    Heung-Woo Park, Sang-Heon Cho & Kyung-Up Min

  5. Rheumatism Research Center, Catholic Institutes of Medical Sciences, The Catholic University of Korea, Seoul, 137-701, Korea

    Mi-La Cho & Sung-Hwan Park

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  1. Eu-Gene Kim
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Correspondence to Chang-Woo Lee.

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Eu-Gene Kim and Hyun-Jin Shin contributed equally to this work.

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Kim, EG., Shin, HJ., Lee, C.G. et al. DNA methylation and not allelic variation regulates STAT6 expression in human T cells. Clin Exp Med 10, 143–152 (2010). https://doi.org/10.1007/s10238-009-0083-8

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  • DOI: https://doi.org/10.1007/s10238-009-0083-8

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