Transcription factor GATA-1 permits survival and maturation of erythroid precursors by preventing apoptosis.

MJ Weiss, SH Orkin - … of the National Academy of Sciences, 1995 - National Acad Sciences
Proceedings of the National Academy of Sciences, 1995National Acad Sciences
The transcription factor GATA-1 recognizes a consensus motif present in regulatory regions
of numerous erythroid-expressed genes. Mouse embryonic stem cells lacking GATA-1
cannot form mature red blood cells in vivo. In vitro differentiation of GATA-1-embryonic stem
cells gives rise to a population of committed erythroid precursors that exhibit developmental
arrest and death. We show here that the demise of GATA-1-erythroid cells is accompanied
by several features characteristics of apoptosis. This process occurs despite normal …
The transcription factor GATA-1 recognizes a consensus motif present in regulatory regions of numerous erythroid-expressed genes. Mouse embryonic stem cells lacking GATA-1 cannot form mature red blood cells in vivo. In vitro differentiation of GATA-1- embryonic stem cells gives rise to a population of committed erythroid precursors that exhibit developmental arrest and death. We show here that the demise of GATA-1- erythroid cells is accompanied by several features characteristics of apoptosis. This process occurs despite normal expression of all known GATA target genes examined, including the erythropoietin receptor, and independent of detectable accumulation of the tumor suppressor protein p53. Thus, in addition to its established role in regulating genes that define the erythroid phenotype, GATA-1 also supports the viability of red cell precursors by suppressing apoptosis. These results illustrate the multifunctional nature of GATA-1 and suggest a mechanism by which other hematopoietic transcription factors may ensure the development of specific lineages.
National Acad Sciences