| First Author | Cao W | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11687 | PubMed ID | 27210293 |
| Mgi Jnum | J:239921 | Mgi Id | MGI:5882025 |
| Doi | 10.1038/ncomms11687 | Citation | Cao W, et al. (2016) CXXC finger protein 1 is critical for T-cell intrathymic development through regulating H3K4 trimethylation. Nat Commun 7:11687 |
| abstractText | T-cell development in the thymus is largely controlled by an epigenetic program, involving in both DNA methylation and histone modifications. Previous studies have identified Cxxc1 as a regulator of both cytosine methylation and histone 3 lysine 4 trimethylation (H3K4me3). However, it is unknown whether Cxxc1 plays a role in thymocyte development. Here we show that T-cell development in the thymus is severely impaired in Cxxc1-deficient mice. Furthermore, we identify genome-wide Cxxc1-binding sites and H3K4me3 modification sites in wild-type and Cxxc1-deficient thymocytes. Our results demonstrate that Cxxc1 directly controls the expression of key genes important for thymocyte survival such as RORgammat and for T-cell receptor signalling including Zap70 and CD8, through maintaining the appropriate H3K4me3 on their promoters. Importantly, we show that RORgammat, a direct target of Cxxc1, can rescue the survival defects in Cxxc1-deficient thymocytes. Our data strongly support a critical role of Cxxc1 in thymocyte development. |
