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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 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 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 Tagoh, H. Articles by Bonifer, C. Search for Related Content PubMed PubMed Citation Articles by Tagoh, H. Articles by Bonifer, C. Related Collections Hematopoiesis and Stem Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS 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 From the Molecular Medicine Unit, University of Leeds, St James's University Hospital, United Kingdom, and the Department of Biology, Beckman Institute of City of Hope, Duarte, CA. 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 found 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 CpG dinucleotides located in the cores of critical transcription factor binding sites, but not in flanking DNA. 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. (Blood. 2004;103:2950-2955) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Hoogenkamp, H. Krysinska, R. Ingram, G. Huang, R. Barlow, D. Clarke, A. Ebralidze, P. Zhang, H. Tagoh, P. N. Cockerill, et al. The Pu.1 Locus Is Differentially Regulated at the Level of Chromatin Structure and Noncoding Transcription by Alternate Mechanisms at Distinct Developmental Stages of Hematopoiesis Mol. Cell. Biol., November 1, 2007; 27(21): 7425 - 7438. [Abstract] [Full Text] [PDF] J. L. Attema, P. Papathanasiou, E. C. Forsberg, J. Xu, S. T. Smale, and I. L. Weissman Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis PNAS, July 24, 2007; 104(30): 12371 - 12376. [Abstract] [Full Text] [PDF] H. Krysinska, M. Hoogenkamp, R. Ingram, N. Wilson, H. Tagoh, P. Laslo, H. Singh, and C. Bonifer A Two-Step, PU.1-Dependent Mechanism for Developmentally Regulated Chromatin Remodeling and Transcription of the c-fms Gene Mol. Cell. Biol., February 1, 2007; 27(3): 878 - 887. [Abstract] [Full Text] [PDF] S. R. L. Young, C. Mumaw, J. A. Marrs, and D. G. Skalnik Antisense Targeting of CXXC Finger Protein 1 Inhibits Genomic Cytosine Methylation and Primitive Hematopoiesis in Zebrafish J. Biol. Chem., December 1, 2006; 281(48): 37034 - 37044. [Abstract] [Full Text] [PDF] F. A. Myers, P. Lefevre, E. Mantouvalou, K. Bruce, C. Lacroix, C. Bonifer, A. W. Thorne, and C. Crane-Robinson Developmental activation of the lysozyme gene in chicken macrophage cells is linked to core histone acetylation at its enhancer elements Nucleic Acids Res., September 1, 2006; 34(14): 4025 - 4035. [Abstract] [Full Text] [PDF] L. M. Kamminga and G. de Haan Cellular Memory and Hematopoietic Stem Cell Aging Stem Cells, May 1, 2006; 24(5): 1143 - 1149. [Abstract] [Full Text] [PDF] T. L. Phelps-Durr, J. Thomas, P. Vahab, and M. C.P. Timmermans Maize rough sheath2 and Its Arabidopsis Orthologue ASYMMETRIC LEAVES1 Interact with HIRA, a Predicted Histone Chaperone, to Maintain knox Gene Silencing and Determinacy during Organogenesis PLANT CELL, November 1, 2005; 17(11): 2886 - 2898. [Abstract] [Full Text] [PDF] P. Lefevre, C. Lacroix, H. Tagoh, M. Hoogenkamp, S. Melnik, R. Ingram, and C. Bonifer Differentiation-dependent Alterations in Histone Methylation and Chromatin Architecture at the Inducible Chicken Lysozyme Gene J. Biol. Chem., July 29, 2005; 280(30): 27552 - 27560. [Abstract] [Full Text] [PDF] H. Szutorisz, C. Canzonetta, A. Georgiou, C.-M. Chow, L. Tora, and N. Dillon Formation of an Active Tissue-Specific Chromatin Domain Initiated by Epigenetic Marking at the Embryonic Stem Cell Stage Mol. Cell. Biol., March 1, 2005; 25(5): 1804 - 1820. [Abstract] [Full Text] [PDF] K. L. Arney and A. G. Fisher Epigenetic aspects of differentiation J. 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