| First Author | Zhang Y | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 12 | Pages | 3248-3261 |
| PubMed ID | 32358021 | Mgi Jnum | J:294658 |
| Mgi Id | MGI:6445338 | Doi | 10.4049/jimmunol.1901471 |
| Citation | Zhang Y, et al. (2020) UHRF1 Controls Thymocyte Fate Decisions through the Epigenetic Regulation of EGR1 Expression. J Immunol 204(12):3248-3261 |
| abstractText | Thymocyte differentiation is a highly complex process that is accompanied by epigenetic changes. Ubiquitin-like containing PHD ring finger 1 (UHRF1) is a critical epigenetic modifier involved in various cellular processes. In this study, we demonstrated that it is highly expressed in T cell precursors of the thymus. Further, its deficiency results in significantly reduced thymocyte cellularity and thymus size in mice. Through systematic analysis based on single-cell RNA sequencing, we found that UHRF1 deficiency thwarts alphabeta T cell lineage development, whereas biasing gammadelta T lineage differentiation dampens the progression of immature single-positive cells. UHRF1 deficiency promotes the IL-17 secreting and RORgammat expression in gammadelta T cell, indicating a Tgammadelta17 phenotype. Further, the analysis of gene-regulatory networks demonstrated that UHRF1 controls the expression of early growth response 1 (EGR1). UHRF1 interacts with DNA methyltransferase 1 (DNMT1) at the CpG promoter region of Egr1 loci and affects the nearby chromatin modifications of H3K9me3 and H3K4me3. Taken together, our results demonstrate that UHRF1 is a key factor that mediates the epigenetic regulation of EGR1 and, consequently, thymocyte fate decisions. |
