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Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-06-2109. This Article Full Text (PDF) All Versions of this Article: 2003-06-2109v1 103/2/562    most recent Alert me when this article is cited Alert me if a correction is posted 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 Nishimura, M. Articles by Okuda, T. Search for Related Content PubMed PubMed Citation Articles by Nishimura, M. Articles by Okuda, T. Social Bookmarking                   What's this? Submitted June 27, 2003 Accepted September 11, 2003 VWRPY-motif-dependent and -independent roles of AML1/Runx1 transcription factor in murine hematopoietic development Motohiro Nishimura, Yoko Fukushima-Nakase, Yasuko Fujita, Mitsushige Nakao, Shogo Toda, Nobuo Kitamura, Tatsuo Abe, and Tsukasa Okuda* Department of Hygiene, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Thoracic Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan Department of Hygiene, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan Department of Hygiene, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Hematology/Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan Department of Thoracic Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan Department of Hygiene, Kyoto Prefectural University of Medicine, Kyoto, Japan * Corresponding author; email: okuda{at}basic.kpu-m.ac.jp. AML1/Runx1 is a frequent target of leukemia-associated gene aberration, and encodes a transcription factor essential for definitive hematopoiesis. We previously reported that the AML1 molecules with trans-activation subdomains retained can rescue in vitro hematopoietic defects of AML1-deficient mouse embryonic stem (ES) cells when expressed by using a knock-in approach. Extending this notion to in vivo conditions, we found that the knock-in ES cell clones with AML1 mutants, which retain trans-activation subdomains but lack a C-terminal repression subdomain including the conserved VWRPY-motif, contribute to hematopoietic tissues in chimera mice. We also found that germline mice homozygous for the mutated AML1 allele, which lacks the VWRPY-motif, have a minimal effect on hematopoietic development, as was observed in control knock-in mice with full-length AML1. On the other hand, reduced cell numbers and deviant CD4-expression were observed during early T-lymphoid ontogeny in the VWRPY-lacking mice, while the contribution to the thymus by the corresponding ES cell clones was inadequate. These findings demonstrate that AML1 with its trans-activating subdomains is both essential and sufficient for hematopoietic development in the context of the entire mouse. In addition, its trans-repression activity, depending on the C-terminal VWRPY-motif, plays a role in early thymocyte development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Setoguchi, M. Tachibana, Y. Naoe, S. Muroi, K. Akiyama, C. Tezuka, T. Okuda, and I. Taniuchi Repression of the Transcription Factor Th-POK by Runx Complexes in Cytotoxic T Cell Development Science, February 8, 2008; 319(5864): 822 - 825. [Abstract] [Full Text] [PDF] Y. Liu, F.-C. Yang, T. Okuda, X. Dong, M. J. Zylka, C.-L. 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