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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2950-2955. Prepublished online as a Blood First Edition Paper on December 18, 2003; DOI 10.1182/blood-2003-09-3323. This Article Full Text (PDF) All Versions of this Article: 2003-09-3323v1 103/8/2950    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 Tagoh, H. Articles by Bonifer, C. Search for Related Content PubMed PubMed Citation Articles by Tagoh, H. Articles by Bonifer, C. Social Bookmarking                   What's this? Submitted October 7, 2003 Accepted November 30, 2003 Dynamic reorganization of chromatin structure and selective DNA-demethylation prior to stable enhancer complex formation during differentiation of primary hematopoietic cells in vitro Hiromi Tagoh, Svitlana Melnik, Pascal Lefevre, Suyinn Chong, Arthur D Riggs, and Constanze Bonifer* Molecular Medicine Unit, University of Leeds, Leeds, United Kingdom Department of Biology, Beckman Institute of City of Hope, Duarte, CA, USA * Corresponding author; email: medcb{at}leeds.ac.uk. In order to gain insights in the true molecular mechanisms involved in cell fate decisions, it is important to study the molecular details of gene activation where such decisions occur, which is at the level of the chromatin structure of individual genes. In the study presented here we addressed this issue and examined the dynamic development of an active chromatin structure at the chicken lysozyme locus during the differentiation of primary myeloid cells from transgenic mouse bone marrow. Using in vivo footprinting we find that stable enhancer complex assembly and high-level gene expression are late events in cell differentiation. However, even before the onset of gene expression and stable transcription factor binding, specific chromatin alterations are observed. This includes changes in DNA topology and the selective demethylation of CpGs located in the cores of critical transcription factor binding sites, but not in flanking regions. These results firmly support the idea that epigenetic programs guiding blood cell differentiation are engraved into the chromatin of lineage specific genes and that such chromatin changes are implemented before cell lineage specification. 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