Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo
- PMID: 12045237
- PMCID: PMC2193547
- DOI: 10.1084/jem.20020656
Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo
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 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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References
-
- Kulessa, H., J. Frampton, and T. Graf. 1995. GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev. 9:1250–1262. - PubMed
-
- Ito, E., T. Toki, H. Ishihara, H. Ohtani, L. Gu, M. Yokoyama, J.D. Engel, and M. Yamamoto. 1993. Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis. Nature. 362:466–468. - PubMed
-
- Martin, D.I., L.I. Zon, G. Mutter, and S.H. Orkin. 1990. Expression of an erythroid transcription factor in megakaryocytic and mast cell lineages. Nature. 344:444–447. - PubMed
-
- Romeo, P.H., M.H. Prandini, V. Joulin, V. Mignotte, M. Prenant, W. Vainchenker, G. Marguerie, and G. Uzan. 1990. Megakaryocytic and erythrocytic lineages share specific transcription factors. Nature. 344:447–449. - PubMed
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