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  • The EMBO Journal (2006) 25, 3586 - 3595
  • doi:10.1038/sj.emboj.7601232

Published online: 13 July 2006

Lineage-specific activators affect bold beta-globin locus chromatin in multipotent hematopoietic progenitors

Stefania Bottardi1,a, Julie Ross1,a, Natacha Pierre-Charles1, Volker Blank2,3 and Eric Milot1,4

  1. Guy-Bernier Research Centre, Maisonneuve-Rosemont Hospital and Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada
  2. Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
  3. Department of Medicine, McGill University, Montreal, Quebec, Canada
  4. Institute for Research in Immunology and Cancer (IRIC), University of Montreal, CP Succursale Centre-ville, Montreal, Quebec, Canada

Correspondence to:

Eric Milot, Guy-Bernier Research Centre, Maisonneuve-Rosemont Hospital and Faculty of Medicine, University of Montreal, 5415 boulevard l'Assomption, Montreal, Quebec, Canada H1T 2M4. Tel.: +1 514 252 3551; Fax: +1 514 252 3430; E-mail: e.milot.1@umontreal.ca

aThese authors contributed equally to this work

Received 19 January 2006; Accepted 20 June 2006

During development, the regulated expression of tissue-specific genes can be preceded by their potentiation, that is, by chromatin activation in progenitor cells. For example, the human beta-like globin genes are potentiated in a gene- and developmental-specific manner in hematopoietic progenitors. Developmental regulation of human beta-gene expression in erythroid cells is mostly determined by transcriptional activators; however, it is not clear how gene-specific potentiation is set in hematopoietic progenitors. Using human and transgenic multipotent hematopoietic progenitors, we demonstrate that human beta-globin locus activation is characterized by TBP, NF-E2, CBP and BRG1 recruitment at both the Locus Control Region and human beta-gene promoter. Our results further indicate that in hematopoietic progenitors, EKLF influences chromatin organization at the human beta-globin locus and is instrumental for human beta-gene potentiation. Thus, we show that lineage-specific transcriptional activators expressed at basal levels in progenitor cells can participate in gene potentiation.

  • Keywords:

    • chromatin,
    • epigenetics,
    • globins,
    • hematopoietic progenitors,
    • transcriptional activators