Article: CD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element

Authors: Athmane Teghanemt, Priyanjali Pulipati, Kara Misel-Wuchter, Kenneth Day, Matthew S Yorek , Ren Yi, Henry L Keen, Christy Au, Thorsten Maretzky, Prajwal Gurung, Dan R Littman, Priya D Issuree

Journal: Nat Commun. 2022 Mar 18;13(1):1477.

Abstract:
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.

Link to journal online: https://www.nature.com/articles/s41467-022-28914-4