Weiss M J, Orkin S H
Children's Hospital, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9623-7. doi: 10.1073/pnas.92.21.9623.
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.
转录因子GATA-1可识别众多红系表达基因调控区域中存在的共有基序。缺乏GATA-1的小鼠胚胎干细胞在体内无法形成成熟红细胞。GATA-1缺陷型胚胎干细胞的体外分化产生了一群定向红系前体细胞，这些细胞表现出发育停滞和死亡。我们在此表明，GATA-1缺陷型红系细胞的死亡伴随着凋亡的几个特征。尽管所检测的所有已知GATA靶基因（包括促红细胞生成素受体）表达正常，且与肿瘤抑制蛋白p53的可检测积累无关，但这一过程仍会发生。因此，除了其在调控定义红系表型的基因方面已确立的作用外，GATA-1还通过抑制凋亡来支持红细胞前体的存活。这些结果说明了GATA-1的多功能性质，并提示了一种其他造血转录因子可能确保特定谱系发育的机制。
