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Blood, 9 July 2009, Vol. 114, No. 2, pp. 299-309. Prepublished online as a Blood First Edition Paper on April 1, 2009; DOI 10.1182/blood-2008-11-191890. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-11-191890v1 114/2/299    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 Hoogenkamp, M. Articles by Bonifer, C. Search for Related Content PubMed PubMed Citation Articles by Hoogenkamp, M. Articles by Bonifer, C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 26, 2008 Accepted March 14, 2009 Early chromatin unfolding by RUNX1 - a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program Maarten Hoogenkamp, Monika Lichtinger, Hanna Krysinska, Christophe Lancrin, Deborah Clarke, Andrew Williamson, Luca Mazzarella, Richard Ingram, Helle Jorgensen, Amanda Fisher, Daniel G. Tenen, Valerie Kouskoff, Georges Lacaud, and Constanze Bonifer* Leeds Institute for Molecular Medicine, University of Leeds, Leeds, United Kingdom Cancer Research UK Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom Cancer Research UK Stem Cell Haematopoiesis Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom MRC Clinical Sciences Centre, Imperial College London School of Medicine, London, United Kingdom Center for Life Sciences, Harvard Medical School, Boston, MA, United States * Corresponding author; email: c.bonifer{at}leeds.ac.uk. At the cellular level, development progresses through successive regulatory states, each characterised by their specific gene expression profile. However, the molecular mechanisms regulating first the priming and then maintenance of gene expression within one developmental pathway are essentially unknown. The hematopoietic system represents a powerful experimental model to address these questions and here we have focused on a regulatory circuit playing a central role in myelopoiesis: the transcription factor PU.1, its target gene Colony-Stimulating-Factor 1 Receptor (Csf1r), and key upstream regulators such as RUNX1. We find that during ontogeny, chromatin unfolding precedes the establishment of active histone marks and the formation of stable transcription factor complexes at the Pu.1 locus and we show that chromatin remodelling is mediated by the transient binding of RUNX1 to Pu.1 cis-elements. By contrast, chromatin reorganisation of Csf1r requires prior expression of PU.1 together with RUNX1 binding. Once the full hematopoietic program is established, stable transcription factor complexes and active chromatin can be maintained without RUNX1. Our experiments therefore demonstrate how individual transcription factors function in a differentiation-stage specific manner to differentially affect the initiation versus maintenance of a developmental program. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Opening act in a hematopoietic program Elaine Dzierzak Blood 2009 114: 229-230. [Full Text] [PDF] This article has been cited by other articles: E. Dzierzak Opening act in a hematopoietic program Blood, July 9, 2009; 114(2): 229 - 230. [Full Text] [PDF]

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