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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5481-5490.
Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2006-11-060491.
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Submitted November 29, 2006
Accepted February 19, 2007
Dynamic regulation of gata factor levels is more
important than their identity
Rita Ferreira, Albert Wai, Ritsuko Shimizu, Nynke Gillemans, Robbert Rottier, Marieke von Lindern, Kinuko Ohneda, Frank Grosveld, Masayuki Yamamoto, and Sjaak Philipsen*
Dept of Cell Biology, Erasmus MC, Rotterdam, Netherlands
Institute of Basic Medical Sciences, and Center for Tsukuba Advanced Reserach Alliance, University of Tsukuba, Tsukuba, Japan
Dept of Hematology, Erasmus MC, Rotterdam, Netherlands
* Corresponding author; email: j.philipsen{at}erasmusmc.nl.
Three Gata transcription factors (Gata1, 2 and 3) are essential for hematopoiesis. These factors are thought to play distinct roles since they do not functionally replace each other. For instance, Gata2 mRNA expression is highly elevated in Gata1 null erythroid cells yet this does not rescue the defect. Here, we test whether Gata2 and -3 transgenes rescue the erythroid defect of Gata1 null mice, if expressed in the appropriate spatio-temporal pattern. Gata1, -2 and -3 transgenes driven by  -globin regulatory elements, directing expression to late stages of differentiation, fail to rescue erythropoiesis in Gata1 null mutants. In contrast, when controlled by Gata1 regulatory elements, directing expression to the early stages of differentiation, Gata1, -2 and -3 do rescue the Gata1 null phenotype. The dramatic increase of endogenous Gata2 mRNA in Gata1 null progenitors is not reflected in Gata2 protein levels, invoking translational regulation. Our data show that the dynamic spatio-temporal regulation of Gata factor levels is more important than their identity, and provide a paradigm for developmental control mechanisms that are hard-wired in cis-regulatory elements.
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