Tanaka Makoto, Zheng Jie, Kitajima Kenji, Kita Keisuke, Yoshikawa Hideki, Nakano Toru
Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Genes Cells. 2004 Dec;9(12):1213-26. doi: 10.1111/j.1365-2443.2004.00796.x.
The molecular interactions between transcription factors and cofactors play crucial roles in various biological processes, including haematopoiesis. FOG-1 is a cognate cofactor of GATA-1, and the FOG-1/GATA-1 complex is essential for the haematopoietic differentiation of erythroid cells and megakaryocytes. In order to elucidate the biological functions of FOG-1 in the different contexts of cell differentiation, we analysed the effects of FOG-1 expression on haematopoietic cell differentiation, using a combination of in vitro differentiation of mouse embryonic stem (ES) cells and conditional gene expression. FOG-1 suppressed the proliferation of primitive and definitive erythroid cells in all stages of differentiation. However, FOG-1 inhibited and enhanced megakaryopoiesis in the early and late differentiation stages, respectively, through different molecular mechanisms. In addition, FOG-1 inhibited the proliferation of ES cells, the molecular mechanism of which differs from those of erythroid and megakaryocytic cells. These results suggest that FOG-1 functions in a cell differentiation context-dependent manner.
转录因子与辅因子之间的分子相互作用在包括造血作用在内的各种生物学过程中发挥着关键作用。FOG-1是GATA-1的同源辅因子，FOG-1/GATA-1复合物对于红细胞和巨核细胞的造血分化至关重要。为了阐明FOG-1在细胞分化不同背景下的生物学功能，我们结合小鼠胚胎干细胞（ES细胞）的体外分化和条件基因表达，分析了FOG-1表达对造血细胞分化的影响。FOG-1在分化的各个阶段均抑制原始和定型红细胞的增殖。然而，FOG-1分别通过不同的分子机制在分化早期和晚期抑制并促进巨核细胞生成。此外，FOG-1抑制ES细胞的增殖，其分子机制与红细胞和巨核细胞的不同。这些结果表明，FOG-1以细胞分化背景依赖的方式发挥作用。
