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Article

  • The EMBO Journal (2006) 25, 1070 - 1080
  • doi:10.1038/sj.emboj.7600997

Published online: 16 February 2006

The mechanism of repression of the myeloid-specific c-fms gene by Pax5 during B lineage restriction

Hiromi Tagoh1, Richard Ingram1,a, Nicola Wilson1,a, Giorgia Salvagiotto2, Alan J Warren3,4, Deborah Clarke1, Meinrad Busslinger2 and Constanze Bonifer1

  1. Division of Experimental Haematology, LIMM, University of Leeds, St James's University Hospital, Leeds, UK
  2. Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria
  3. MRC Laboratory of Molecular Biology, Cambridge, UK
  4. Department of Haematology, University of Cambridge, Cambridge, UK

Correspondence to:

Constanze Bonifer, Leeds Institute of Molecular Medicine, The JIF Building, St James University Hospital, University of Leeds, Leeds LS9 7TF, UK. Tel.: +44 113 343 8525; Fax: +44 113 343 8702; E-mail: c.bonifer@leeds.ac.uk

aThese authors contributed equally to this work

Received 20 September 2005; Accepted 19 January 2006

The transcription factor Pax5 (BSAP) is required for the expression of a B-cell-specific genetic program and for B-cell differentiation, and also to suppress genes of alternative lineages. The molecular mechanism by which repression of myeloid genes occurs during early B-lineage restriction is unknown and in this study we addressed this question. One of the genes repressed by Pax5 in B cells is the colony-stimulating factor receptor 1 gene (csf1r or c-fms). We examined the changes in chromatin caused by Pax5 activity, and we show that Pax5 is directly recruited to c-fms resulting in the rapid loss of RNA polymerase II binding, followed by loss of transcription factor binding and DNaseI hypersensitivity at all cis-regulatory elements. We also show that Pax5 targets the basal transcription machinery of c-fms by interacting with a binding site within the major transcription start sites. Our results support a model by which Pax5 does not lead to major alterations in chromatin modification, but inhibits transcription by interfering with the action of myeloid transcription factors.

  • Keywords:

    • B-lineage restriction,
    • c-fms,
    • chromatin,
    • gene silencing,
    • Pax5