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

David Whyatt, Fokke Lindeboom, Alar Karis, Rita Ferreira, Eric Milot, Rudi Hendriks, Marella de Bruijn, An Langeveld, Joost Gribnau, Frank Grosveld () and Sjaak Philipsen
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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

Nature, 2000, vol. 406, issue 6795, 519-524

Abstract: 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.

Date: 2000
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DOI: 10.1038/35020086

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