| First Author | Zhou XF | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 49 | Pages | 20083-8 |
| PubMed ID | 23169648 | Mgi Jnum | J:192327 |
| Mgi Id | MGI:5464933 | Doi | 10.1073/pnas.1214704109 |
| Citation | Zhou XF, et al. (2012) TRIM28 mediates chromatin modifications at the TCRalpha enhancer and regulates the development of T and natural killer T cells. Proc Natl Acad Sci U S A 109(49):20083-8 |
| abstractText | T-cell receptor-alpha (TCRalpha) rearrangement in CD4(+)CD8(+) double-positive immature thymocytes is a prerequisite for production of alphabeta T cells and invariant natural killer T cells. This developmental event is regulated by the TCRalpha enhancer (Ealpha), which induces chromatin modification and recruitment of the recombination-activating proteins Rag1 and Rag2. However, the molecular mechanism underlying the activation and long-range action of Ealpha remains incompletely understood. We show here that the chromatin-modifying factor TRIM28 is highly expressed in double-positive thymocytes and persistently phosphorylated at serine 473. TRIM28 binds to Ealpha and induces histone 3 lysine 4 trimethylation in the Ealpha and distant regions of the TCRalpha locus, coupled with recruitment of Rag proteins. T-cell-conditional ablation of TRIM28 impaired TCRalpha gene rearrangement and compromised the development of alphabeta T cells and invariant natural killer T cells. These findings establish TRIM28 as a unique regulator of thymocyte development and highlight an epigenetic mechanism involving TRIM28-mediated active chromatin modification in the TCRalpha locus. |
