Article
- The EMBO Journal (2006) 25, 1070 - 1080
- doi:10.1038/sj.emboj.7600997
Published online: 16 February 2006
Subject Categories:
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
- Division of Experimental Haematology, LIMM, University of Leeds, St James's University Hospital, Leeds, UK
- Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria
- MRC Laboratory of Molecular Biology, Cambridge, UK
- 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
Abstract
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



