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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 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 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 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. Related Collections Hematopoiesis and Stem Cells Platelets and Thrombopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis Christos Gekas1,*, Katrin E. Rhodes1,*, Laurraine M. Gereige1, Hildur Helgadottir2, Roberto Ferrari3, Siavash K. Kurdistani3, Encarnación Montecino-Rodriguez4, Rhonda Bassel-Duby5, Eric Olson5, Andrei V. Krivtsov6, Scott Armstrong2,6, Stuart H. Orkin2,68, Matteo Pellegrini1,9, and Hanna K. A. Mikkola1,911 1 Department of Molecular, Cell and Developmental Biology, University of California–Los Angeles; 2 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 3 Department of Biologic Chemistry, University of California–Los Angeles; 4 Department of Pathology and Laboratory Medicine, University of California–Los Angeles; 5 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas; 6 Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, MA; 7 Howard Hughes Medical Institute, Boston, MA; 8 Harvard Stem Cell Institute, Boston, MA; 9 Molecular Biology Institute, University of California–Los Angeles; 10 Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at University of California–Los Angeles; and 11 Jonsson Comprehensive Cancer Center, University of California–Los Angeles The basic helix-loop-helix 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, whereas platelet size was increased and the platelet shape and granularity were altered. Furthermore, megakaryopoiesis was severely impaired in vitro. Chromatin immunoprecipitation microarray hybridization 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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