Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo

C Yu, AB Cantor, H Yang, C Browne… - The Journal of …, 2002 - rupress.org
C Yu, AB Cantor, H Yang, C Browne, RA Wells, Y Fujiwara, SH Orkin
The Journal of experimental medicine, 2002rupress.org
Transcription factor GATA-1 reprograms immature myeloid cells to three different
hematopoietic lineages-erythroid cells, megakaryocytes, and eosinophils. GATA-1 is
essential for maturation of erythroid and megakaryocytic precursors, as revealed by gene
targeting in mice. Here we demonstrate that deletion of a high-affinity GATA-binding site in
the GATA-1 promoter, an element presumed to mediate positive autoregulation of GATA-1
expression, leads to selective loss of the eosinophil lineage. These findings suggest that …
Transcription factor GATA-1 reprograms immature myeloid cells to three different hematopoietic lineages-erythroid cells, megakaryocytes, and eosinophils. GATA-1 is essential for maturation of erythroid and megakaryocytic precursors, as revealed by gene targeting in mice. Here we demonstrate that deletion of a high-affinity GATA-binding site in the GATA-1 promoter, an element presumed to mediate positive autoregulation of GATA-1 expression, leads to selective loss of the eosinophil lineage. These findings suggest that GATA-1 is required for specification of this lineage during hematopoietic development. Mice lacking the ability to produce eosinophils should prove useful in ascertaining the role of eosinophils in a variety of inflammatory or allergic disorders.
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