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Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2002-01-0182. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-01-0182v1 100/8/2769    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Osawa, M. Articles by Iwama, A. Search for Related Content PubMed PubMed Citation Articles by Osawa, M. Articles by Iwama, A. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 October 2002, Vol. 100, No. 8, pp. 2769-2777 HEMATOPOIESIS Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis Mitsujiro Osawa, Tomoyuki Yamaguchi, Yukio Nakamura, Shin Kaneko, Masafumi Onodera, Ken-ichi Sawada, Armin Jegalian, Hong Wu, Hiromitsu Nakauchi, and Atsushi Iwama From the Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and Core Research for Evolutional Science and Technology of Japan Science and Technology, Japan; the Department of Internal Medicine III, Akita University School of Medicine, Japan; the Molecular Biology Institute, Department of Molecular and Medical Pharmacology, and Howard Hughes Medical Institute, UCLA School of Medicine, Los Angeles, CA; and the Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Japan. In the search for genes expressed in hematopoietic stem cells, we identified that the expression of Gfi-1B (growth factor independence-1B) is highly restricted to hematopoietic stem cells, erythroblasts, and megakaryocytes. Gfi-1 and Gfi-1B are zinc finger proteins that share highly conserved SNAG and 6 zinc finger domains. Gfi-1 has been characterized as an oncogene involved in lymphoid malignancies in mice. In contrast, role of Gfi-1B in hematopoiesis has not been well characterized. In this study, we analyzed its function in human hematopoiesis. Enforced expression of Gfi-1B in human CD34+ hematopoietic progenitors induced a drastic expansion of erythroblasts in an erythropoietin-independent manner. Expression of Gfi-1B did not promote erythroid commitment, but enhanced proliferation of immature erythroblasts. Erythroblasts expanded by exogenous Gfi-1B, however, failed to differentiate beyond proerythroblast stage and showed massive apoptosis. These biologic effects of Gfi-1B were mediated through its zinc finger domain, but not by the SNAG or non-zinc finger domain. Proliferation of erythroblasts was associated with sustained expression of GATA-2 but not of GATA-1, indicating a potential link between Gfi-1B and GATA family regulators. Importantly, the function of Gfi-1B to modulate transcription was dependent on promoter context. In addition, activation of transcription of an artificial promoter was mediated through its zinc finger domain. These findings establish Gfi-1B as a novel erythroid regulator and reveal its specific involvement in the regulation of erythroid cell growth through modulating erythroid-specific gene expression. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Ogaeri, K. Eto, M. Otsu, H. Ema, and H. 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