Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo.
Journal:
J. Exp. Med. 2002 JunAuthors:
Yu C, Cantor AB, Yang H, Browne C, Wells RA, Fujiwara Y, Orkin SH
Abstract
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
...[more] 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.[less]
Mesh Headings:
Animals, Base Sequence, Cell Differentiation, Cell Lineage, DNA-Binding Proteins, Eosinophils, Erythroid-Specific DNA-Binding Factors, Erythropoiesis, GATA1 Transcription Factor, Gene Expression Regulation, Interleukin-5, Leukopoiesis, Male, Mast Cells, Mice, Mice, Transgenic, Molecular Sequence Data, Mutagenesis, Site-Directed, Promoter Regions, Genetic, RNA, Messenger, Response Elements, Sequence Deletion, Transcription Factors