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

Clinical and Experimental Medicine
Eu-Gene KimChang-Woo Lee

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....Continue Reading

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Citations

Jul 11, 2012·Seminars in Immunopathology·Xiumei Hong, Xiaobin Wang
Mar 28, 2012·Current Allergy and Asthma Reports·Stephanie Lovinsky-Desir, Rachel L Miller
Mar 26, 2013·American Journal of Respiratory Cell and Molecular Biology·Yan ShangWan-yee Tang
Jun 5, 2012·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Marek GodavaRadek Vrtel
Nov 29, 2013·Epigenomics·Gabrielle A LockettWilfried Karmaus
Nov 19, 2013·Clinical Reviews in Allergy & Immunology·Yu LiuQianjin Lu
Aug 6, 2015·Respiratory Research·Dorota StefanowiczTillie-Louise Hackett
Feb 9, 2018·International Journal of Molecular Sciences·Sabrina IqbalWilfried J J Karmaus
Jun 12, 2013·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Marek GodavaRadek Vodicka
Jun 22, 2018·Omics : a Journal of Integrative Biology·Matija PecakTanja Kunej
Aug 16, 2011·Current Opinion in Allergy and Clinical Immunology·Gerard H Koppelman, Martijn C Nawijn
Jun 22, 2018·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Yujuan ZhangElizabeth D Mellins

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