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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4188-4197. Prepublished online as a Blood First Edition Paper on September 6, 2007; DOI 10.1182/blood-2007-07-100883. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-07-100883v1 110/13/4188    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 Nottingham, W. T. Articles by de Bruijn, M. F. T. R. Search for Related Content PubMed PubMed Citation Articles by Nottingham, W. T. Articles by de Bruijn, M. F. T. R. Related Collections Hematopoiesis and Stem Cells Gene Expression Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer Wade T. Nottingham1, Andrew Jarratt1, Matthew Burgess1, Caroline L. Speck1, Jan-Fang Cheng2,3, Shyam Prabhakar2,3, Eddy M. Rubin2,3, Pik-Shan Li1, Jackie Sloane-Stanley1, John Kong-a-San4, and Marella F. T. R. de Bruijn1 1 Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom; 2 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA; 3 United States Department of Energy Joint Genome Institute, Walnut Creek, CA; and 4 Department of Cell Biology, Erasmus Medical Center, Rotterdam, The Netherlands The transcription factor Runx1/AML1 is an important regulator of hematopoiesis and is critically required for the generation of the first definitive hematopoietic stem cells (HSCs) in the major vasculature of the mouse embryo. As a pivotal factor in HSC ontogeny, its transcriptional regulation is of high interest but is largely undefined. In this study, we used a combination of comparative genomics and chromatin analysis to identify a highly conserved 531-bp enhancer located at position + 23.5 in the first intron of the 224-kb mouse Runx1 gene. We show that this enhancer contributes to the early hematopoietic expression of Runx1. Transcription factor binding in vivo and analysis of the mutated enhancer in transient transgenic mouse embryos implicate Gata2 and Ets proteins as critical factors for its function. We also show that the SCL/Lmo2/Ldb-1 complex is recruited to the enhancer in vivo. Importantly, transplantation experiments demonstrate that the intronic Runx1 enhancer targets all definitive HSCs in the mouse embryo, suggesting that it functions as a crucial cis-regulatory element that integrates the Gata, Ets, and SCL transcriptional networks to initiate HSC generation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. 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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] E. Yi Ni Lam, J. Y. M. Chau, M. L. Kalev-Zylinska, T. M. Fountaine, R. S. Mead, C. J. Hall, P. S. Crosier, K. E. Crosier, and M. Vega Flores Zebrafish runx1 promoter-EGFP transgenics mark discrete sites of definitive blood progenitors Blood, February 5, 2009; 113(6): 1241 - 1249. [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] J.-R. Landry, S. Kinston, K. Knezevic, M. F.T.R. de Bruijn, N. Wilson, W. T. Nottingham, M. Peitz, F. Edenhofer, J. E. Pimanda, K. Ottersbach, et al. Runx genes are direct targets of Scl/Tal1 in the yolk sac and fetal liver Blood, March 15, 2008; 111(6): 3005 - 3014. 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