Tsang A P, Fujiwara Y, Hom D B, Orkin S H
Division of Hematology-Oncology, Children's Hospital and Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes Dev. 1998 Apr 15;12(8):1176-88. doi: 10.1101/gad.12.8.1176.
GATA transcription factors are required for the differentiation of diverse cell types in several species. Recent evidence suggests that their biologic activities may be modulated through interaction with multitype zinc finger proteins, such as Friend of GATA-1 (FOG) and U-shaped (Ush). In cell culture, FOG cooperates with the hematopoietic transcription factor GATA-1 to promote erythroid and megakaryocytic differentiation. We show here that mice lacking FOG die during mid-embryonic development with severe anemia. FOG-/- erythroid cells display a marked, but partial, blockage of maturation, reminiscent of GATA-1- erythroid precursors. In contrast to GATA-1 deficiency, however, megakaryocytes fail to develop in the absence of FOG. Although the FOG-/- erythroid phenotype supports the proposed role of FOG as a GATA-1 cofactor in vivo, the latter finding points to a pivotal, GATA-1-independent requirement for FOG in megakaryocyte development from the bipotential erythroid/megakaryocytic progenitor. We speculate that FOG and other FOG-like proteins serve as complex cofactors that act through both GATA-dependent and GATA-independent mechanisms.
GATA转录因子在多个物种中多种细胞类型的分化过程中是必需的。最近的证据表明，它们的生物学活性可能通过与多种类型的锌指蛋白相互作用来调节，比如GATA-1的伙伴（FOG）和U型蛋白（Ush）。在细胞培养中，FOG与造血转录因子GATA-1协同作用，促进红细胞和巨核细胞的分化。我们在此表明，缺乏FOG的小鼠在胚胎发育中期因严重贫血而死亡。FOG基因敲除的红细胞显示出明显但部分的成熟阻滞，这与GATA-1基因敲除的红细胞前体相似。然而，与GATA-1缺乏不同的是，在没有FOG的情况下巨核细胞无法发育。尽管FOG基因敲除的红细胞表型支持了FOG在体内作为GATA-1辅因子的假定作用，但后一发现表明，在双潜能红细胞/巨核细胞祖细胞向巨核细胞发育过程中，FOG存在关键的、不依赖GATA-1的需求。我们推测，FOG和其他类似FOG的蛋白作为复杂的辅因子，通过依赖GATA和不依赖GATA的机制发挥作用。
