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Blood, 28 May 2009, Vol. 113, No. 22, pp. 5456-5465. Prepublished online as a Blood First Edition Paper on April 3, 2009; DOI 10.1182/blood-2009-01-200048. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-01-200048v1 113/22/5456    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 Wilson, N. K. Articles by Göttgens, B. Search for Related Content PubMed PubMed Citation Articles by Wilson, N. K. Articles by Göttgens, B. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS The transcriptional program controlled by the stem cell leukemia gene Scl/Tal1 during early embryonic hematopoietic development Nicola K. Wilson1, Diego Miranda-Saavedra1, Sarah Kinston1, Nicolas Bonadies1, Samuel D. Foster1, Fernando Calero-Nieto1, Mark A. Dawson1, Ian J. Donaldson2, Stephanie Dumon3, Jonathan Frampton3, Rekin's Janky4, Xiao-Hong Sun5, Sarah A. Teichmann4, Andrew J. Bannister6, and Berthold Göttgens1 1 University of Cambridge Department of Haematology, Cambridge Institute for Medical Research, Cambridge, United Kingdom; 2 Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom; 3 Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, United Kingdom; 4 Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom; 5 Oklahoma Medical Research Foundation, University of Oklahoma, Oklahoma City; and 6 Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Pathology, Cambridge, United Kingdom The basic helix-loop-helix transcription factor Scl/Tal1 controls the development and subsequent differentiation of hematopoietic stem cells (HSCs). However, because few Scl target genes have been validated to date, the underlying mechanisms have remained largely unknown. In this study, we have used ChIP-Seq technology (coupling chromatin immunoprecipitation with deep sequencing) to generate a genome-wide catalog of Scl-binding events in a stem/progenitor cell line, followed by validation using primary fetal liver cells and comprehensive transgenic mouse assays. Transgenic analysis provided in vivo validation of multiple new direct Scl target genes and allowed us to reconstruct an in vivo validated network consisting of 17 factors and their respective regulatory elements. By coupling ChIP-Seq in model cell lines with in vivo transgenic validation and sophisticated bioinformatic analysis, we have identified a widely applicable strategy for the reconstruction of stem cell regulatory networks in which biologic material is otherwise limiting. Moreover, in addition to revealing multiple previously unrecognized links to known HSC regulators, as well as novel links to genes not previously implicated in HSC function, comprehensive transgenic analysis of regulatory elements provided substantial new insights into the transcriptional control of several important hematopoietic regulators, including Cbfa2t3h/Eto2, Cebpe, Nfe2, Zfpm1/Fog1, Erg, Mafk, Gfi1b, and Myb. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Roeder and F. Radtke Stem cell biology meets systems biology Development, November 1, 2009; 136(21): 3525 - 3530. [Abstract] [Full Text] [PDF] L. A. Steiner, Y. Maksimova, V. Schulz, C. Wong, D. Raha, M. C. Mahajan, S. M. Weissman, and P. G. Gallagher Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes Mol. Cell. Biol., October 15, 2009; 29(20): 5399 - 5412. [Abstract] [Full Text] [PDF]

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