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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4532-4541. Prepublished online as a Blood First Edition Paper on March 7, 2008; DOI 10.1182/blood-2007-10-116343. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-10-116343v1 111/9/4532    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 Schüler, A. Articles by Stocking, C. Search for Related Content PubMed PubMed Citation Articles by Schüler, A. Articles by Stocking, C. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate Andrea Schüler1,*, Maike Schwieger1,*, Afra Engelmann1, Kristoffer Weber1, Stefan Horn1, Ursula Müller1, Michael A. Arnold2, Eric N. Olson2, and Carol Stocking1 1 Heinrich-Pette-Institute, Hamburg, Germany; and 2 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas Mef2c is a MADS (MCM1-agamous–deficient serum response factor) transcription factor best known for its role in muscle and cardiovascular development. A causal role of up-regulated MEF2C expression in myelomonocytic acute myeloid leukemia (AML) has recently been demonstrated. Due to the pronounced monocytic component observed in Mef2c-induced AML, this study was designed to assess the importance of Mef2c in normal myeloid differentiation. Analysis of bone marrow (BM) cells manipulated to constitutively express Mef2c demonstrated increased monopoiesis at the expense of granulopoiesis, whereas BM isolated from Mef2c/– mice showed reduced levels of monocytic differentiation in response to cytokines. Mechanistic studies showed that loss of Mef2c expression correlated with reduced levels of transcripts encoding c-Jun, but not PU.1, C/EBP, or JunB transcription factors. Inhibiting Jun expression by short-interfering RNA impaired Mef2c-mediated inhibition of granulocyte development. Moreover, retroviral expression of c-Jun in BM cells promoted monocytic differentiation. The ability of Mef2c to modulate cell-fate decisions between monocyte and granulocyte differentiation, coupled with its functional sensitivity to extracellular stimuli, demonstrate an important role in immunity—and, consistent with findings of other myeloid transcription factors, a target of oncogenic lesions in AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Schwieger, A. Schuler, M. Forster, A. Engelmann, M. A. Arnold, R. Delwel, P. J. Valk, J. Lohler, R. K. Slany, E. N. Olson, et al. Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C Blood, September 17, 2009; 114(12): 2476 - 2488. [Abstract] [Full Text] [PDF] C. Gekas, K. E. Rhodes, L. M. Gereige, H. Helgadottir, R. Ferrari, S. K. Kurdistani, E. Montecino-Rodriguez, R. Bassel-Duby, E. Olson, A. V. Krivtsov, et al. Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis Blood, April 9, 2009; 113(15): 3461 - 3471. [Abstract] [Full Text] [PDF]

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