Coreceptor gene imprinting governs thymocyte lineage fate
Adoro, Stanley and McCaughtry, Thomas and Erman, Batu and Alag, Amala and Van Laethem, François and Park, Jung-Hyun and Tai, Xuguang and Kimura, Motoko and Wang, Lie and Grinberg, Alex and Kubo, Masato and Bosselut, Remy and Love, Paul and Singer, Alfred (2012) Coreceptor gene imprinting governs thymocyte lineage fate. The EMBO Journal, 31 (2). pp. 366-377. ISSN 0261-4189 (print) ; 1460-2075 (online)
Official URL: http://dx.doi.org/10.1038/emboj.2011.388
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.
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