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Publication : Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cells.

First Author  Makar KW Year  2003
Journal  Nat Immunol Volume  4
Issue  12 Pages  1183-90
PubMed ID  14595437 Mgi Jnum  J:265236
Mgi Id  MGI:6200132 Doi  10.1038/ni1004
Citation  Makar KW, et al. (2003) Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cells. Nat Immunol 4(12):1183-90
abstractText  How T cells regulate interleukin 4 (IL-4) expression is not completely understood. We show here that single-positive thymocytes express IL-4, but attenuate GATA-3 expression, recruit DNA methyltransferases (Dnmts) to the Il4-Il13 locus and downregulate IL-4 expression as they mature into T cells. Type 2 polarization blocks Dnmt1 recruitment, enhances histone H3 Lys4 methylation (indicative of accessible chromatin) and initiates DNA demethylation of the locus. Dnmt1-/- CD4 and CD8 T cells derepress IL-4 expression considerably, demethylate DNA and increase H3 Lys4 methylation without affecting GATA-3 expression, demonstrating that Dnmt1 and DNA methylation are essential for proper Il4 regulation. These results indicate that Dnmts, DNA and histone methylation, and transcription factors 'collaborate' to determine appropriate Il4 expression patterns.
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