| First Author | Adoro S | Year | 2012 |
| Journal | EMBO J | Volume | 31 |
| Issue | 2 | Pages | 366-77 |
| PubMed ID | 22036949 | Mgi Jnum | J:180236 |
| Mgi Id | MGI:5305887 | Doi | 10.1038/emboj.2011.388 |
| Citation | Adoro S, et al. (2011) Coreceptor gene imprinting governs thymocyte lineage fate. EMBO J 31(2):366-77 |
| abstractText | Immature thymocytes are bipotential cells that are signalled during positive selection to become either helper- or cytotoxic-lineage T cells. By tracking expression of lineage determining transcription factors during positive selection, we now report that the Cd8 coreceptor gene locus co-opts any coreceptor protein encoded within it to induce thymocytes to express the cytotoxic-lineage factor Runx3 and to adopt the cytotoxic-lineage fate, findings we refer to as 'coreceptor gene imprinting'. Specifically, encoding CD4 proteins in the endogenous Cd8 gene locus caused major histocompatibility complex class II-specific thymocytes to express Runx3 during positive selection and to differentiate into CD4(+) cytotoxic-lineage T cells. Our findings further indicate that coreceptor gene imprinting derives from the dynamic regulation of specific cis Cd8 gene enhancer elements by positive selection signals in the thymus. Thus, for coreceptor-dependent thymocytes, lineage fate is determined by Cd4 and Cd8 coreceptor gene loci and not by the specificity of T-cell antigen receptor/coreceptor signalling. This study identifies coreceptor gene imprinting as a critical determinant of lineage fate determination in the thymus. |
