Epigenetic silencing of the c-fms locus during B-lymphopoiesis occurs in discrete steps and is reversible

Hiromi Tagoh, Alexandra Schebesta, Pascal Lefevre, Nicola Wilson, David Hume, Meinrad Busslinger, Constanze Bonifer

Research output: Contribution to journalArticlepeer-review

Abstract

The murine c-fms (Csf1r) gene encodes the macrophage colony-stimulating factor receptor, which is essential for macrophage development. It is expressed at a low level in haematopoietic stem cells and is switched off in all non-macrophage cell types. To examine the role of chromatin structure in this process we studied epigenetic silencing of c-fms during B-lymphopoiesis. c-fms chromatin in stem cells and multipotent progenitors is in the active conformation and bound by transcription factors. A similar result was obtained with specified common myeloid and lymphoid progenitor cells. In developing B cells, c-fms chromatin is silenced in distinct steps, whereby first the binding of transcription factors and RNA expression is lost, followed by a loss of nuclease accessibility. Interestingly, regions of de novo DNA methylation in B cells overlap with an intronic antisense transcription unit that is differently regulated during lymphopoiesis. However, even at mature B cell stages, c-fms chromatin is still in a poised conformation and c-fms expression can be re-activated by conditional deletion of the transcription factor Pax5.
Original languageEnglish
Pages (from-to)4275-85
Number of pages11
JournalEMBO Journal
Volume23
Issue number21
DOIs
Publication statusPublished - 27 Oct 2004

Keywords

  • Animals
  • B-Lymphocytes
  • Chromatin
  • DNA Methylation
  • Epigenesis, Genetic
  • Gene Expression Regulation
  • Gene Silencing
  • Genes, fms
  • Histones
  • Lymphopoiesis
  • Mice
  • Nucleic Acid Conformation
  • Pluripotent Stem Cells
  • Promoter Regions, Genetic
  • RNA, Antisense
  • Transcription Factors

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