转录因子GATA-1在造血系统中的作用(综述)

转录因子GATA-1为正常红细胞发育和分化成熟所必需。GATA-1的表达严格限制于造血细胞系,主要调控红系的增殖和分化,对巨核系、肥大细胞系及嗜酸性粒细胞系也起一定的作用。GATA-1参与自身启动子的正调节,而且GATA-1和PU.1可以通过交互作用抑制各自的功能;GATA-1与红系Kr櫣ppel样因子(EKLF)、FKLF-2、SCL、生长因子骨形态生成蛋白(BMP-4)及其他GATA转录因子之间存在相互调控作用。GATA-1可在急性非淋巴细胞性白血病等多种类型白血病中表达,它的表达还可影响急性髓性白血病的预后。GATA-1还与遗传性球形红细胞增多症、伴有严重贫血的多发性骨髓瘤的发病机制有关。     

Developmental regulation of a cloned adult beta-globin gene in transgenic mice

At different stages of mammalian development, distinct embryonic, fetal and adult haemoglobins are synthesized in erythroid cells, a process termed haemoglobin switching. The cellular and molecular mechanisms controlling haemoglobin switching have been intensively studied, but remain poorly understood. To study the developmental regulation of globin gene expression, we have produced transgenic mice in which cloned globin genes are present in erythroid cells throughout development. Recently, we reported that adult mice in several transgenic lines carrying a hybrid mouse/human adult beta-globin gene, expressed the gene in a correct tissue-specific manner. This finding raised the question of whether an exogenous globin gene could also be subject to appropriate stage-specific regulation. We report here that the hybrid beta-globin gene, like the endogenous adult beta-globin genes, is inactive in yolk sac-derived embryonic erythroid cells and is expressed for the first time in fetal liver erythroid cells. Our results indicate that a stage-specific pattern of expression can be conferred by cis-acting regulatory elements closely linked to an adult beta-globin gene. They also suggest that the embryonic and adult beta-globin genes in the mouse are activated (or repressed) by distinct trans-acting regulatory factors present in embryonic, fetal and adult erythroid cells.