| First Author | Helmin KA | Year | 2020 |
| Journal | J Clin Invest | Volume | 130 |
| Issue | 12 | Pages | 6571-6587 |
| PubMed ID | 32897881 | Mgi Jnum | J:338188 |
| Mgi Id | MGI:7510271 | Doi | 10.1172/JCI137712 |
| Citation | Helmin KA, et al. (2020) Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function. J Clin Invest 130(12):6571-6587 |
| abstractText | Tregs require Foxp3 expression and induction of a specific DNA hypomethylation signature during development, after which Tregs persist as a self-renewing population that regulates immune system activation. Whether maintenance DNA methylation is required for Treg lineage development and stability and how methylation patterns are maintained during lineage self-renewal remain unclear. Here, we demonstrate that the epigenetic regulator ubiquitin-like with plant homeodomain and RING finger domains 1 (Uhrf1) is essential for maintenance of methyl-DNA marks that stabilize Treg cellular identity by repressing effector T cell transcriptional programs. Constitutive and induced deficiency of Uhrf1 within Foxp3+ cells resulted in global yet nonuniform loss of DNA methylation, derepression of inflammatory transcriptional programs, destabilization of the Treg lineage, and spontaneous inflammation. These findings support a paradigm in which maintenance DNA methylation is required in distinct regions of the Treg genome for both lineage establishment and stability of identity and suppressive function. |
