IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v406y2000i6795d10.1038_35020086.html
   My bibliography  Save this article

An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells

Author

Listed:
  • David Whyatt

    (Division of Molecular Carcinogenesis The Netherlands Cancer Institute)

  • Fokke Lindeboom

    (Erasmus University, Medical Genetics Centre)

  • Alar Karis

    (Erasmus University, Medical Genetics Centre)

  • Rita Ferreira

    (Erasmus University, Medical Genetics Centre)

  • Eric Milot

    (Erasmus University, Medical Genetics Centre)

  • Rudi Hendriks

    (Erasmus University, Medical Genetics Centre)

  • Marella de Bruijn

    (Erasmus University, Medical Genetics Centre)

  • An Langeveld

    (Erasmus University, Medical Genetics Centre)

  • Joost Gribnau

    (Erasmus University, Medical Genetics Centre)

  • Frank Grosveld

    (Erasmus University, Medical Genetics Centre)

  • Sjaak Philipsen

    (Erasmus University, Medical Genetics Centre)

Abstract

GATA-1 is a tissue-specific transcription factor that is essential for the production of red blood cells1,2. Here we show that overexpression of GATA-1 in erythroid cells inhibits their differentiation, leading to a lethal anaemia. Using chromosome-X-inactivation of a GATA-1 transgene and chimaeric animals, we show that this defect is intrinsic to erythroid cells, but nevertheless cell nonautonomous. Usually, cell nonautonomy is thought to reflect aberrant gene function in cells other than those that exhibit the phenotype3. On the basis of our data, we propose an alternative mechanism in which a signal originating from wild-type erythroid cells restores normal differentiation to cells overexpressing GATA-1 in vivo. The existence of such a signalling mechanism indicates that previous interpretations of cell-nonautonomous defects may be erroneous in some cases and may in fact assign gene function to incorrect cell types.

Suggested Citation

  • David Whyatt & Fokke Lindeboom & Alar Karis & Rita Ferreira & Eric Milot & Rudi Hendriks & Marella de Bruijn & An Langeveld & Joost Gribnau & Frank Grosveld & Sjaak Philipsen, 2000. "An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells," Nature, Nature, vol. 406(6795), pages 519-524, August.
    • Handle: RePEc:nat:nature:v:406:y:2000:i:6795:d:10.1038_35020086
    DOI: 10.1038/35020086
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35020086
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/35020086?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:406:y:2000:i:6795:d:10.1038_35020086. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.