| Autor: |
Tom M. McCaughtry, Alex Grinberg, Amala Alag, Alfred Singer, Lie Wang, Jung-Hyun Park, Rémy Bosselut, Motoko Y. Kimura, Xuguang Tai, François Van Laethem, Stanley Adoro, Batu Erman, Paul E. Love, Masato Kubo |
| Rok vydání: |
2011 |
| Předmět: |
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| Zdroj: |
The EMBO Journal. 31:366-377 |
| ISSN: |
0261-4189 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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