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Blood, 9 April 2009, Vol. 113, No. 15, pp. 3461-3471. Prepublished online as a Blood First Edition Paper on February 11, 2009; DOI 10.1182/blood-2008-07-167577. This Article Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2008-07-167577v1 113/15/3461    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 Gekas, C. Articles by Mikkola, H. K A Search for Related Content PubMed PubMed Citation Articles by Gekas, C. Articles by Mikkola, H. K A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 10, 2008 Accepted December 14, 2008 Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B cell homeostasis Christos Gekas, Katrin E Rhodes, Laurraine M Gereige, Hildur Helgadottir, Roberto Ferrari, Siavash K Kurdistani, Encarnacion Montecino-Rodriguez, Rhonda Bassel-Duby, Eric Olson, Andrei V Krivtsov, Scott Armstrong, Stuart H Orkin, Matteo Pellegrini, and Hanna K A Mikkola* Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, United States Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States Department of Biological Chemistry, UCLA, Los Angeles, CA, United States Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, United States Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, United States Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, MA, United States Harvard Stem Cell Institute, Boston, MA, United States Molecular Biology Institute, UCLA, Los Angeles, CA, United States Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA, Los Angeles, CA, United States * Corresponding author; email: hmikkola{at}mcdb.ucla.edu. The bHLH transcription factor stem cell leukemia gene (Scl) is a master regulator for hematopoiesis essential for hematopoietic specification and proper differentiation of the erythroid and megakaryocyte lineages. However, the critical downstream targets of Scl remain undefined. Here, we identified a novel Scl target gene, transcription factor myocyte enhancer factor 2 C (Mef2C) from Sclfl/fl fetal liver progenitor cell lines. Analysis of Mef2C-/- embryos showed that Mef2C, in contrast to Scl, is not essential for specification into primitive or definitive hematopoietic lineages. However, adult VavCre+Mef2Cfl/fl mice exhibited platelet defects similar to those observed in Scl deficient mice. The platelet counts were reduced, while platelet size was increased and the platelet shape and granularity was altered. Furthermore, megakaryopoiesis was severely impaired in vitro. ChIP-on-chip analysis revealed that Mef2C is directly regulated by Scl in megakaryocytic cells, but not in erythroid cells. In addition, an Scl independent requirement for Mef2C in B-lymphoid homeostasis was observed in Mef2C-deficient mice, characterized as severe age-dependent reduction of specific B cell progenitor populations reminiscent of premature aging. In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages. 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]

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