Coreceptor gene imprinting governs thymocyte lineage fate
EMBO JOURNAL, cilt.31, sa.2, ss.366-377, 2012 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 31 Sayı: 2
- Basım Tarihi: 2012
- Doi Numarası: 10.1038/emboj.2011.388
- Dergi Adı: EMBO JOURNAL
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.366-377
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır
Özet
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. The EMBO Journal (2012) 31, 366-377. doi:10.1038/emboj.2011.388; Published online 28 October 2011