| First Author | Gamper CJ | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 4 | Pages | 2267-76 |
| PubMed ID | 19625655 | Mgi Jnum | J:151787 |
| Mgi Id | MGI:4355274 | Doi | 10.4049/jimmunol.0802960 |
| Citation | Gamper CJ, et al. (2009) Identification of DNA methyltransferase 3a as a T cell receptor-induced regulator of Th1 and Th2 differentiation. J Immunol 183(4):2267-76 |
| abstractText | Ag-specific T cell cytokine expression is dictated by the context in which TCR engagement occurs. Recently it has become clear that epigenetic changes play a role in this process. DNA methyltransferase 3a (DNMT3a) is a de novo methyltransferase important to the epigenetic control of cell fate. We have determined that DNMT3a expression is increased following TCR engagement and that costimulation mitigates DNMT3a protein expression. T cells lacking DNMT3a simultaneously express IFN-gamma and IL-4 after expansion under nonbiasing conditions. While global methylation of DNA from wild-type and knockout T cells is similar, DNMT3a-null T cells demonstrate selective hypomethylation of both the Il4 and Ifng loci after activation. Such hypomethylated knockout Th2 cells retain a greater capacity to express IFN-gamma protein when they are subsequently exposed to Th1-biasing conditions. Based on these findings we propose that DNMT3a is a key participant in regulating T cell polarization at the molecular level by promoting stable selection of a context-specific cell fate through methylation of selective targets in T cells. |
