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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3005-3014. Prepublished online as a Blood First Edition Paper on January 9, 2008; DOI 10.1182/blood-2007-07-098830. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-07-098830v1 111/6/3005    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 Landry, J.-R. Articles by Gottgens, B. Search for Related Content PubMed PubMed Citation Articles by Landry, J.-R. Articles by Gottgens, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 3, 2007 Accepted December 5, 2007 Runx genes are direct targets of Scl/Tal1 in the yolk sac and fetal liver Josette-Renee Landry, Sarah Kinston, Kathy Knezevic, Marella F.T.R. de Bruijn, Nicola Wilson, Wade T. Nottingham, Michael Peitz, Frank Edenhofer, John E Pimanda, Katrin Ottersbach, and Berthold Gottgens* Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom Stem Cell Engineering Group, Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn and Hertie Foundation, Bonn, Germany * Corresponding author; email: bg200{at}cam.ac.uk. Transcription factors such as Scl/Tal1, Lmo2 and Runx1 are essential for the development of hematopoietic stem cells (HSCs). However, the precise mechanisms by which these factors interact to form transcriptional networks, as well as the identity of the genes downstream of these regulatory cascades remain largely unknown. To this end, we generated an Scl-/- yolk sac cell line to identify candidate Scl target genes by global expression profiling following re-introduction of a TAT-Scl fusion protein. Bioinformatics analysis resulted in the identification of nine candidate Scl target transcription factor genes, including Runx1 and Runx3. Chromatin immunoprecipitation confirmed that both Runx genes are direct targets of Scl in the fetal liver and that Runx1 is also occupied by Scl in the yolk sac. Furthermore, binding of an Scl-Lmo2-Gata2 complex was demonstrated to occur on the regions flanking the conserved E-boxes of the Runx1 loci and was shown to transactivate the Runx1 element. Together our data provides a key component of the transcriptional network of early haematopoiesis by identifying downstream targets of Scl that can explain key aspects of the early Scl-/- phenotype. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Hoogenkamp, M. Lichtinger, H. Krysinska, C. Lancrin, D. Clarke, A. Williamson, L. Mazzarella, R. Ingram, H. Jorgensen, A. Fisher, et al. Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program Blood, July 9, 2009; 114(2): 299 - 309. [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] T. Bee, E. L.K. Ashley, S. R.B. Bickley, A. Jarratt, P.-S. Li, J. Sloane-Stanley, B. Gottgens, and M. F.T.R. de Bruijn The mouse Runx1 +23 hematopoietic stem cell enhancer confers hematopoietic specificity to both Runx1 promoters Blood, May 21, 2009; 113(21): 5121 - 5124. [Abstract] [Full Text] [PDF] F. Cerisoli, L. Cassinelli, G. Lamorte, S. Citterio, F. Bertolotti, M. C. Magli, and S. Ottolenghi Green fluorescent protein transgene driven by Kit regulatory sequences is expressed in hematopoietic stem cells Haematologica, March 1, 2009; 94(3): 318 - 325. [Abstract] [Full Text] [PDF] O. Ben-Ami, N. Pencovich, J. Lotem, D. Levanon, and Y. Groner A regulatory interplay between miR-27a and Runx1 during megakaryopoiesis PNAS, January 6, 2009; 106(1): 238 - 243. [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]

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