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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1908-1916. Prepublished online as a Blood First Edition Paper on October 19, 2006; DOI 10.1182/blood-2006-05-023226. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-05-023226v1 109/5/1908    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 Chan, W. Y. I. Articles by Göttgens, B. Search for Related Content PubMed PubMed Citation Articles by Chan, W. Y. I. Articles by Göttgens, B. Related Collections Hematopoiesis and Stem Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS The paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl–/– phenotype Wan Y. I. Chan1, George A. Follows1, Georges Lacaud2, John E. Pimanda1, Josette-Renee Landry1, Sarah Kinston1, Kathy Knezevic1, Sandie Piltz1, Ian J. Donaldson1, Laure Gambardella1, Fred Sablitzky3, Anthony R. Green1, Valerie Kouskoff2, and Berthold Göttgens1 1 Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, United Kingdom; 2 Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom; 3 Institute of Genetics, University of Nottingham, United Kingdom Transcription factors are key regulators of hematopoietic stem cells (HSCs), yet the molecular mechanisms that control their expression are largely unknown. Previously, we demonstrated that expression of Scl/Tal1, a transcription factor required for the specification of HSCs, is controlled by Ets and GATA factors. Here we characterize the molecular mechanisms controlling expression of Lyl1, a paralog of Scl also required for HSC function. Two closely spaced promoters directed expression to hematopoietic progenitor, megakaryocytic, and endothelial cells in transgenic mice. Conserved binding sites required for promoter activity were bound in vivo by GATA-2 and the Ets factors Fli1, Elf1, Erg, and PU.1. However, despite coregulation of Scl and Lyl1 by the same Ets and GATA factors, Scl expression was initiated prior to Lyl1 in embryonic stem (ES) cell differentiation assays. Moreover, ectopic expression of Scl but not Lyl1 rescued hematopoietic differentiation in Scl–/– ES cells, thus providing a molecular explanation for the vastly different phenotypes of Scl–/– and Lyl1–/– mouse embryos. Furthermore, coregulation of Scl and Lyl1 later during development may explain the mild phenotype of Scl–/– adult HSCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-R. Landry, N. Bonadies, S. Kinston, K. Knezevic, N. K. Wilson, S. H. Oram, M. Janes, S. Piltz, M. Hammett, J. Carter, et al. Expression of the leukemia oncogene Lmo2 is controlled by an array of tissue-specific elements dispersed over 100 kb and bound by Tal1/Lmo2, Ets, and Gata factors Blood, June 4, 2009; 113(23): 5783 - 5792. [Abstract] [Full Text] [PDF] N. K. Wilson, D. Miranda-Saavedra, S. Kinston, N. Bonadies, S. D. Foster, F. Calero-Nieto, M. A. Dawson, I. J. Donaldson, S. Dumon, J. Frampton, et al. The transcriptional program controlled by the stem cell leukemia gene Scl/Tal1 during early embryonic hematopoietic development Blood, May 28, 2009; 113(22): 5456 - 5465. [Abstract] [Full Text] [PDF] J. E. Pimanda, W. Y. I. Chan, N. K. Wilson, A. M. Smith, S. Kinston, K. Knezevic, M. E. Janes, J.-R. Landry, A. Kolb-Kokocinski, J. Frampton, et al. Endoglin expression in blood and endothelium is differentially regulated by modular assembly of the Ets/Gata hemangioblast code Blood, December 1, 2008; 112(12): 4512 - 4522. [Abstract] [Full Text] [PDF] F. Liu and R. Patient Genome-Wide Analysis of the Zebrafish ETS Family Identifies Three Genes Required for Hemangioblast Differentiation or Angiogenesis Circ. Res., November 7, 2008; 103(10): 1147 - 1154. [Abstract] [Full Text] [PDF] R. J. Wozniak, S. Keles, J. J. Lugus, K. H. Young, M. E. Boyer, T. M. Tran, K. Choi, and E. H. Bresnick Molecular Hallmarks of Endogenous Chromatin Complexes Containing Master Regulators of Hematopoiesis Mol. Cell. Biol., November 1, 2008; 28(21): 6681 - 6694. [Abstract] [Full Text] [PDF] A. M. Smith, M.-J. Sanchez, G. A. Follows, S. Kinston, I. J. Donaldson, A. R. Green, and B. Gottgens A novel mode of enhancer evolution: The Tal1 stem cell enhancer recruited a MIR element to specifically boost its activity Genome Res., September 1, 2008; 18(9): 1422 - 1432. [Abstract] [Full Text] [PDF] J. E. Pimanda, K. Ottersbach, K. Knezevic, S. Kinston, W. Y. I. Chan, N. K. Wilson, J.-R. Landry, A. D. Wood, A. Kolb-Kokocinski, A. R. Green, et al. Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development PNAS, November 6, 2007; 104(45): 17692 - 17697. [Abstract] [Full Text] [PDF] K. D. Johnson, M. E. Boyer, J.-A. Kang, A. Wickrema, A. B. Cantor, and E. H. Bresnick Friend of GATA-1-independent transcriptional repression: a novel mode of GATA-1 function Blood, June 15, 2007; 109(12): 5230 - 5233. [Abstract] [Full Text] [PDF] R. J. Wozniak, M. E. Boyer, J. A. Grass, Y. Lee, and E. H. Bresnick Context-dependent GATA Factor Function: COMBINATORIAL REQUIREMENTS FOR TRANSCRIPTIONAL CONTROL IN HEMATOPOIETIC AND ENDOTHELIAL CELLS J. Biol. Chem., May 11, 2007; 282(19): 14665 - 14674. [Abstract] [Full Text] [PDF]

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