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http://hdl.handle.net/2445/177169
Title: | CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha}gene expression in early human thymopoiesis and leukemia |
Author: | González-García, Sara García-Peydró, Marina Martín-Gayo, Enrique Ballestar Tarín, Esteban Esteller, Manel Bornstein, Rafael Pompa, José Luis de la Ferrando, Adolfo A. Toribio, María L. |
Keywords: | Expressió gènica Leucèmia Immunologia Timus (Glàndula) Gene expression Leukemia Immunology Thymus |
Issue Date: | 13-Apr-2009 |
Publisher: | Rockefeller University Press |
Abstract: | Notch1 activation is essential for T-lineage specification of lymphomyeloid progenitors seeding the thymus. Progression along the T cell lineage further requires cooperative signaling provided by the interleukin 7 receptor (IL-7R), but the molecular mechanisms responsible for the dynamic and lineage-specific regulation of IL-7R during thymopoiesis are unknown. We show that active Notch1 binds to a conserved CSL-binding site in the human IL7R gene promoter and critically regulates IL7R transcription and IL-7R alpha chain (IL-7Ralpha) expression via the CSL-MAML complex. Defective Notch1 signaling selectively impaired IL-7Ralpha expression in T-lineage cells, but not B-lineage cells, and resulted in a compromised expansion of early human developing thymocytes, which was rescued upon ectopic IL-7Ralpha expression. The pathological implications of these findings are demonstrated by the regulation of IL-7Ralpha expression downstream of Notch1 in T cell leukemias. Thus, Notch1 controls early T cell development, in part by regulating the stage- and lineage-specific expression of IL-7Ralpha. |
Note: | Reproducció del document publicat a: https://doi.org/10.1084/jem.20081922 |
It is part of: | Journal of Experimental Medicine, 2009, vol. 206, num. 4, p. 779-791 |
URI: | http://hdl.handle.net/2445/177169 |
Related resource: | https://doi.org/10.1084/jem.20081922 |
ISSN: | 0022-1007 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) |
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