| First Author | Dobenecker MW | Year | 2015 |
| Journal | J Exp Med | Volume | 212 |
| Issue | 3 | Pages | 297-306 |
| PubMed ID | 25687282 | Mgi Jnum | J:222033 |
| Mgi Id | MGI:5643879 | Doi | 10.1084/jem.20141499 |
| Citation | Dobenecker MW, et al. (2015) Coupling of T cell receptor specificity to natural killer T cell development by bivalent histone H3 methylation. J Exp Med 212(3):297-306 |
| abstractText | The fidelity of T cell immunity depends greatly on coupling T cell receptor signaling with specific T cell effector functions. Here, we describe a chromatin-based mechanism that enables integration of TCR specificity into definite T cell lineage commitment. Using natural killer T cells (iNKT cell) as a model of a T cell subset that differentiates in response to specific TCR signaling, we identified a key role of histone H3 lysine 27 trimethylation (H3K27me3) in coupling iNKT cell TCR specificity with the generation of iNKT cells. We found that the Zbtb16/PLZF gene promoter that drives iNKT cell differentiation possesses a bivalent chromatin state characterized by the simultaneous presence of negative and positive H3K27me3 and H3K4me3 modifications. Depletion of H3K27me3 at the Zbtb16/PLZF promoter leads to uncoupling of iNKT cell development from TCR specificity and is associated with accumulation of iNKT-like CD4(+) cells that express a non-iNKT cell specific T cell repertoire. In turn, stabilization of H3K27me3 leads to a drastic reduction of the iNKT cell population. Our data suggest that H3K27me3 levels at the bivalent Zbtb16/PLZF gene define a threshold enabling precise coupling of TCR specificity to lineage commitment. |
