Chromatin Modifications in Hematopoietic Multipotent and Committed Progenitors Are Independent of Gene Subnuclear Positioning Relative to Repressive Compartments§

Authors

  • Claire Guillemin,

    1. Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche [UMR] 8104), Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, U567, Paris, France
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  • Marta Maleszewska,

    1. Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, U662, Paris, France
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  • Adeline Guais,

    1. Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche [UMR] 8104), Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, U567, Paris, France
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  • Jérôme Maës,

    1. Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, U662, Paris, France
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  • Marie-Christine Rouyez,

    1. Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche [UMR] 8104), Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, U567, Paris, France
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  • Azzedine Yacia,

    1. Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche [UMR] 8104), Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, U567, Paris, France
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  • Serge Fichelson,

    1. Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche [UMR] 8104), Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, U567, Paris, France
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  • Michele Goodhardt,

    1. Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, U662, Paris, France
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  • Claire Francastel

    Corresponding author
    1. Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche [UMR] 8104), Paris, France
    2. Institut National de la Santé et de la Recherche Médicale, U567, Paris, France
    • Institut Cochin, Département d'Hématologie, INSERM U567–CNRS UMR 8104, Maternité Port-Royal, 5ème étage, 123, Boulevard Port-Royal, 75014 Paris, France
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    • Telephone: 33-1-53-10-43-84; Fax: 33-1-43-25-11-67


  • Author contributions: C.G.: performance of research, data analysis and interpretation; M.M., A.G., and J.M.: performance of research; M.-C.R.: contributions to real-time PCR; A.Y.: contributions to expansion of erythroid progenitors; S.F.: provision of study material; M.G.: data analysis and interpretation, manuscript drafting; C.F.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript. C.G. and M.M. contributed equally to this work.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSExpress October 30, 2008.

Abstract

To further clarify the contribution of nuclear architecture in the regulation of gene expression patterns during differentiation of human multipotent cells, we analyzed expression status, histone modifications, and subnuclear positioning relative to repressive compartments, of hematopoietic loci in multipotent and lineage-committed primary human hematopoietic progenitors. We report here that positioning of lineage-affiliated loci relative to pericentromeric heterochromatin compartments (PCH) is identical in multipotent cells from various origins and is unchanged between multipotent and lineage-committed hematopoietic progenitors. However, during differentiation of multipotent hematopoietic progenitors, changes in gene expression and histone modifications at these loci occur in committed progenitors, prior to changes in gene positioning relative to pericentromeric heterochromatin compartments, detected at later stages in precursor and mature cells. Therefore, during normal human hematopoietic differentiation, changes in gene subnuclear location relative to pericentromeric heterochromatin appear to be dictated by whether the gene will be permanently silenced or activated, rather than being predictive of commitment toward a given lineage. STEM CELLS2009;27:108–115

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