| First Author | Bandyopadhyay S | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 2 | Pages | 233-45 |
| PubMed ID | 24190972 | Mgi Jnum | J:207682 |
| Mgi Id | MGI:5559379 | Doi | 10.1128/MCB.00902-13 |
| Citation | Bandyopadhyay S, et al. (2014) Tle4 regulates epigenetic silencing of gamma interferon expression during effector T helper cell tolerance. Mol Cell Biol 34(2):233-45 |
| abstractText | In response to suboptimal activation, T cells become hyporesponsive, with a severely reduced capacity to proliferate and produce cytokines upon reencounter with antigen. Chromatin analysis of T cells made tolerant by use of different in vitro and in vivo approaches reveals that the expression of gamma interferon (IFN-gamma) is epigenetically silenced in anergic effector TH1 cells. In those T cells, calcium signaling triggers the expression of Tle4, a member of the Groucho family of corepressors, which is then recruited to a distal regulatory element in the Ifng locus and causes the establishment of repressive epigenetic marks at the Ifng gene regulatory elements. Consequently, impaired Tle4 activity results in a markedly reduced capacity to inhibit IFN-gamma production in tolerized T cells. We propose that Blimp1-dependent recruitment of Tle4 to the Ifng locus causes epigenetic silencing of the expression of the Ifng gene in anergic TH1 cells. These results define a novel function of Groucho family corepressors in peripheral T cells and demonstrate that specific mechanisms are activated in tolerant T helper cells to directly repress expression of effector cytokines, supporting the hypothesis that stable epigenetic imprinting contributes to the maintenance of the tolerance-associated hyporesponsive phenotype in T cells. |
