| First Author | Teghanemt A | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 1477 |
| PubMed ID | 35304452 | Mgi Jnum | J:333574 |
| Mgi Id | MGI:7259423 | Doi | 10.1038/s41467-022-28914-4 |
| Citation | Teghanemt A, et al. (2022) CD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element. Nat Commun 13(1):1477 |
| abstractText | The epigenetic patterns that are established during early thymic development might determine mature T cell physiology and function, but the molecular basis and topography of the genetic elements involved are not fully known. Here we show, using the Cd4 locus as a paradigm for early developmental programming, that DNA demethylation during thymic development licenses a novel stimulus-responsive element that is critical for the maintenance of Cd4 gene expression in effector T cells. We document the importance of maintaining high CD4 expression during parasitic infection and show that by driving transcription, this stimulus-responsive element allows for the maintenance of histone H3K4me3 levels during T cell replication, which is critical for preventing de novo DNA methylation at the Cd4 promoter. A failure to undergo epigenetic programming during development leads to gene silencing during effector T cell replication. Our study thus provides evidence of early developmental events shaping the functional fitness of mature effector T cells. |
