Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

c-FMS chromatin structure and expression in normal and leukaemic myelopoiesis

Oncogene volume 24, pages 3643–3651 (2005)Cite this article

Abstract

The macrophage colony-stimulating factor receptor is encoded by the c-FMS gene, and it has been suggested that altered regulation of c-FMS expression may contribute to leukaemic transformation. c-FMS is expressed in pluripotent haemopoietic precursor cells and is subsequently upregulated during monocytic differentiation, but downregulated during granulopoiesis. We have examined transcription factor occupancy and aspects of chromatin structure of the critical c-FMS regulatory element located within the second intron (FIRE – fms intonic regulatory element) during normal and leukaemic myelopoiesis. Granulocytic differentiation from normal and leukaemic precursors is accompanied by loss of transcription factors at FIRE and downregulated c-FMS expression. The presence of AML1-ETO in leukaemic cells does not prevent this disassembly. In nonleukaemic cells, granulocytic differentiation is accompanied by reversal to a chromatin fine structure characteristic of c-FMS-nonexpressing cells. In addition, we show that low-level expression of the gene in leukaemic blast cells and granulocytes does not associate with increased CpG methylation across the c-FMS locus.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Alcalay M, Meani N, Gelmetti V, Fantozzi A, Fagioli M, Orleth A, Riganelli D, Sebastiani C, Cappelli E, Casciari C, Sciurpi MT, Mariano AR, Minardi SP, Luzi L, Muller H, Di Fiore PP, Frosina G and Pelicci PG . (2003). J. Clin. Invest., 112, 1751–1761.

  • Boultwood J, Rack K, Kelly S, Madden J, Sakaguchi AY, Wang LM, Oscier DG, Buckle VJ and Wainscoat JS . (1991). Proc. Natl. Acad. Sci. USA, 88, 6176–6180.

  • Casas S, Nagy B, Elonen E, Aventin A, Larramendy ML, Sierra J, Ruutu T and Knuutila S . (2003). Leukemia Lymphoma, 44, 1935–1941.

  • Chen HH, Kontaraki J, Bonifer C and Riggs AD . (2001). Sci. STKE, 2001, PL1.

  • Dahl R, Walsh JC, Lancki D, Laslo P, Iyer SR, Singh H and Simon MC . (2003). Nat. Immunol., 10, 1029–1036.

  • Dai XM, Ryan GR, Hapel AJ, Dominguez MG, Russell RG, Kapp S, Sylvestre V and Stanley ER . (2002). Blood, 99, 111–120.

  • Debernardi S, Lillington DM, Chaplin T, Tomlinson S, Amess J, Rohatiner A, Lister TA and Young BD . (2003). Genes Chromosomes Cancer, 37, 149–158.

  • Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C, Minucci S and Pelicci PG . (2002). Science, 295, 1079–1082.

  • Downing JR . (1999). Br. J. Haematol., 106, 296–308.

  • Follows GA, Tagoh H, Lefevre P, Hodge D, Morgan GJ and Bonifer C . (2003a). EMBO J., 22, 2798–2809.

  • Follows GA, Tagoh H, Lefevre P, Morgan GJ and Bonifer C . (2003b). Nucleic Acids Res., 31, 5805–5816.

  • Gisselbrecht S, Fichelson S, Sola B, Bordereaux D, Hampe A, Andre C, Galibert F and Tambourin P . (1987). Nature, 329, 259–261.

  • Heidenreich O, Krauter J, Riehle H, Hadwiger P, John M, Heil G, Vornlocher HP and Nordheim A . (2003). Blood, 101, 3157–3163.

  • Himes SR, Tagoh H, Goonetilleke N, Sasmono T, Oceandy D, Clark R, Bonifer C and Hume DA . (2001). J. Leukocyte Biol., 70, 812–820.

  • Kelly LM and Gilliland DG . (2002). Annu. Rev. Genomics Hum. Genet., 3, 179–198.

  • Kontaraki J, Chen HH, Riggs A and Bonifer C . (2000). Genes Dev., 14, 2106–2122.

  • Lichtenberger C, Zakeri S, Baier K, Willheim M, Holub M and Reinisch W . (1999). J. Immunol. Methods, 227, 75–84.

  • McGlynn H, Kapelko K, Baker A, Burnett A and Padua RA . (1997). Leukemia Res., 21, 919–923.

  • Morris JF, Hromas R and Rauscher III FJ . (1994). Mol. Cell. Biol., 14, 1786–1795.

  • Rosenbauer F, Wagner K, Kutok JL, Iwasaki H, Le Beau MM, Okuno Y, Akashi K, Fiering S and Tenen DG . (2004). Nat. Genet, 36, 624–630.

  • Rountree MR, Bachman KE, Herman JG and Baylin SB . (2001). Oncogene, 20, 3156–3165.

  • Sariban E, Mitchell T and Kufe D . (1985). Nature, 316, 64–66.

  • Sasmono RT, Oceandy D, Pollard JW, Tong W, Pavli P, Wainwright BJ, Ostrowski MC, Himes SR and Hume DA . (2003). Blood, 101, 1155–1163.

  • Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT and Stanley ER . (1985). Cell, 41, 665–676.

  • Springall F, O’Mara S, Shounan Y, Todd A, Ford D and Iland H . (1993). Leukemia, 7, 978–985.

  • Tagoh H, Himes R, Clarke D, Leenen PJ, Riggs AD, Hume D and Bonifer C . (2002). Genes Dev., 16, 1721–1737.

  • Tagoh H, Schebesta A, Lefevre P, Wilson N, Hume D, Busslinger M and Bonifer C . (2004). EMBO J., 23, 4275–4285.

Download references

Acknowledgements

GAF is a Leukaemia Research Fund Bennett Fellow, HT is funded by the Kay Kendall Leukaemia Fund. Research in CB's laboratory is funded by the MRC, Wellcome Trust and Leukaemia Research Fund.

Author information

Authors and Affiliations

  1. Molecular Medicine Unit, St James's University Hospital, Leeds, UK

    George Alexander Follows, Hiromi Tagoh, Svitlana Melnik, Erica de Wynter, Pascal Lefevre & Constanze Bonifer

  2. Academic Unit of Haematology and Oncology, Leeds General Infirmary, Leeds, UK

    George Alexander Follows, Stephen John Richards & Gareth John Morgan

  3. Department of Cytogenetics, St James's University Hospital, Leeds, UK

    Helen Dickinson

Authors
  1. George Alexander Follows
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiromi Tagoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen John Richards
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Svitlana Melnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helen Dickinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Erica de Wynter
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pascal Lefevre
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gareth John Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Constanze Bonifer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Alexander Follows.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Follows, G., Tagoh, H., Richards, S. et al. c-FMS chromatin structure and expression in normal and leukaemic myelopoiesis. Oncogene 24, 3643–3651 (2005). https://doi.org/10.1038/sj.onc.1208655

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208655

Keywords

This article is cited by

Search

Advanced search

Quick links