Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 478K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yücel, R. Articles by Möröy, T. Search for Related Content PubMed PubMed Citation Articles by Yücel, R. Articles by Möröy, T. Social Bookmarking                      What's this?

Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, D-45122 Essen, Germany

Address correspondence to Tarik Möröy, Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, D-45122 Essen, Germany. Phone: 49-201-723-3380; Fax: 49-201-723-5904; E-mail: moeroey{at}uni-essen.de

In the thymus, several steps of proliferative expansion and selection coordinate the maturation of precursors into antigen-specific T cells. Here we identify the transcriptional repressor Gfi1 as an important regulator of this maturation process. Mice lacking Gfi1 show reduced thymic cellularity due to an increased cell death rate, lack of proliferation, and a differentiation block in the very early uncommitted CD4^-/CD8^-/c-Kit⁺ cytokine-dependent T cell progenitors that have not yet initiated VDJ recombination. In addition, Gfi1-deficient mice show increased major histocompatibility complex class I–restricted positive selection and develop significantly more CD8⁺ cells suggesting a requirement of Gfi1 for a correct CD4/CD8 lineage decision. Absence of Gfi1 correlates with high level expression of the genes for lung Krüppel-like factor (LKLF), inhibitor of DNA binding (Id)1 and Id2, suggesting the existence of new regulatory pathways in pre-T cell development and thymic selection in which Gfi1 acts upstream of LKLF as well as the E-proteins, which are negatively regulated by Id1 and Id2.

Key Words: zinc finger protein • T cell differentiation • apoptosis • lineage skewing • helix-loop-helix proteins

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Lauritsen, J.-P. H., Kurella, S., Lee, S.-Y., Lefebvre, J. M., Rhodes, M., Alberola-Ila, J., Wiest, D. L. (2008). Egr2 Is Required for Bcl-2 Induction during Positive Selection. J. Immunol. 181: 7778-7785 [Abstract] [Full Text]  
• Rathinam, C., Lassmann, H., Mengel, M., Klein, C. (2008). Transcription Factor Gfi1 Restricts B Cell-Mediated Autoimmunity. J. Immunol. 181: 6222-6229 [Abstract] [Full Text]  
• Baron, M.-L., Gauchat, D., La Motte-Mohs, R., Kettaf, N., Abdallah, A., Michiels, T., Zuniga-Pflucker, J.-C., Sekaly, R.-P. (2008). TLR Ligand-Induced Type I IFNs Affect Thymopoiesis. J. Immunol. 180: 7134-7146 [Abstract] [Full Text]  
• De La Luz Sierra, M., Gasperini, P., McCormick, P. J., Zhu, J., Tosato, G. (2007). Transcription factor Gfi-1 induced by G-CSF is a negative regulator of CXCR4 in myeloid cells. Blood 110: 2276-2285 [Abstract] [Full Text]  
• Xu, W., Kee, B. L. (2007). Growth factor independent 1B (Gfi1b) is an E2A target gene that modulates Gata3 in T-cell lymphomas. Blood 109: 4406-4414 [Abstract] [Full Text]  
• Pepple, K. L., Anderson, A. E., Frankfort, B. J., Mardon, G. (2007). A Genetic Screen in Drosophila for Genes Interacting With senseless During Neuronal Development Identifies the Importin moleskin. Genetics 175: 125-141 [Abstract] [Full Text]  
• Marteijn, J. A. F., van der Meer, L. T., Van Emst, L., de Witte, T., Jansen, J. H., van der Reijden, B. A. (2007). Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes. Blood 109: 100-108 [Abstract] [Full Text]  
• Zhu, J., Jankovic, D., Grinberg, A., Guo, L., Paul, W. E. (2006). Gfi-1 plays an important role in IL-2-mediated Th2 cell expansion. Proc. Natl. Acad. Sci. USA 103: 18214-18219 [Abstract] [Full Text]  
• Guidos, C. J. (2006). Synergy between the pre-T cell receptor and Notch: cementing the {alpha}{beta} lineage choice. JEM 203: 2233-2237 [Abstract] [Full Text]  
• Schwartz, R., Engel, I., Fallahi-Sichani, M., Petrie, H. T., Murre, C. (2006). Gene expression patterns define novel roles for E47 in cell cycle progression, cytokine-mediated signaling, and T lineage development. Proc. Natl. Acad. Sci. USA 103: 9976-9981 [Abstract] [Full Text]  
• Jafar-Nejad, H., Tien, A.-C., Acar, M., Bellen, H. J. (2006). Senseless and Daughterless confer neuronal identity to epithelial cells in the Drosophila wing margin. Development 133: 1683-1692 [Abstract] [Full Text]  
• Schuh, A. H., Tipping, A. J., Clark, A. J., Hamlett, I., Guyot, B., Iborra, F. J., Rodriguez, P., Strouboulis, J., Enver, T., Vyas, P., Porcher, C. (2005). ETO-2 Associates with SCL in Erythroid Cells and Megakaryocytes and Provides Repressor Functions in Erythropoiesis. Mol. Cell. Biol. 25: 10235-10250 [Abstract] [Full Text]  
• Duan, Z., Zarebski, A., Montoya-Durango, D., Grimes, H. L., Horwitz, M. (2005). Gfi1 Coordinates Epigenetic Repression of p21Cip/WAF1 by Recruitment of Histone Lysine Methyltransferase G9a and Histone Deacetylase 1. Mol. Cell. Biol. 25: 10338-10351 [Abstract] [Full Text]  
• Terra, R., Louis, I., Le Blanc, R., Ouellet, S., Zuniga-Pflucker, J. C., Perreault, C. (2005). T-cell generation by lymph node resident progenitor cells. Blood 106: 193-200 [Abstract] [Full Text]  
• Vassen, L., Fiolka, K., Mahlmann, S., Möröy, T. (2005). Direct transcriptional repression of the genes encoding the zinc-finger proteins Gfi1b and Gfi1 by Gfi1b. Nucleic Acids Res 33: 987-998 [Abstract] [Full Text]  
• Jafar-Nejad, H., Bellen, H. J. (2004). Gfi/Pag-3/Senseless Zinc Finger Proteins: a Unifying Theme?. Mol. Cell. Biol. 24: 8803-8812 [Full Text]  
• Kazanjian, A., Wallis, D., Au, N., Nigam, R., Venken, K. J. T., Cagle, P. T., Dickey, B. F., Bellen, H. J., Gilks, C. B., Grimes, H. L. (2004). Growth Factor Independence-1 Is Expressed in Primary Human Neuroendocrine Lung Carcinomas and Mediates the Differentiation of Murine Pulmonary Neuroendocrine Cells. Cancer Res. 64: 6874-6882 [Abstract] [Full Text]  
• Yucel, R., Kosan, C., Heyd, F., Moroy, T. (2004). Gfi1:Green Fluorescent Protein Knock-in Mutant Reveals Differential Expression and Autoregulation of the Growth Factor Independence 1 (Gfi1) Gene during Lymphocyte Development. J. Biol. Chem. 279: 40906-40917 [Abstract] [Full Text]  
• Hertzano, R., Montcouquiol, M., Rashi-Elkeles, S., Elkon, R., Yucel, R., Frankel, W. N., Rechavi, G., Moroy, T., Friedman, T. B., Kelley, M. W., Avraham, K. B. (2004). Transcription profiling of inner ears from Pou4f3ddl/ddl identifies Gfi1 as a target of the Pou4f3 deafness gene. Hum Mol Genet 13: 2143-2153 [Abstract] [Full Text]  
• Misslitz, A., Pabst, O., Hintzen, G., Ohl, L., Kremmer, E., Petrie, H. T., Forster, R. (2004). Thymic T Cell Development and Progenitor Localization Depend on CCR7. JEM 200: 481-491 [Abstract] [Full Text]  
• Tabrizifard, S., Olaru, A., Plotkin, J., Fallahi-Sichani, M., Livak, F., Petrie, H. T. (2004). Analysis of Transcription Factor Expression during Discrete Stages of Postnatal Thymocyte Differentiation. J. Immunol. 173: 1094-1102 [Abstract] [Full Text]  
• Doan, L. L., Porter, S. D., Duan, Z., Flubacher, M. M., Montoya, D., Tsichlis, P. N., Horwitz, M., Gilks, C. B., Grimes, H. L. (2004). Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells. Nucleic Acids Res 32: 2508-2519 [Abstract] [Full Text]  
• Shanker, A., Auphan-Anezin, N., Chomez, P., Giraudo, L., Eynde, B. V. d., Schmitt-Verhulst, A.-M. (2004). Thymocyte-Intrinsic Genetic Factors Influence CD8 T Cell Lineage Commitment and Affect Selection of a Tumor-Reactive TCR. J. Immunol. 172: 5069-5077 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS