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

Research output: Contribution to journalArticle

Authors

  • H Tagoh
  • A Schebesta
  • P Lefevre
  • N Wilson
  • D Hume
  • M Busslinger

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)4275-85
Number of pages11
JournalThe EMBO journal
Volume23
Issue number21
Publication statusPublished - 27 Oct 2004