红系造血抑制是苯血液毒性主要表现，其机制还不明确。申请者前期研究发现，苯的酚类代谢物短期处理能显著抑制K562细胞的红系分化，并抑制红系分化关键转录因子GATA2和GATA1的表达，降低GATA1在珠蛋白基因的占领。而在红系分化过程中，GATA2和GATA1的表达会发生所谓“GATA因子转换”，造成红系分化关键基因的GATA位点结合的GATA2被GATA1替换，GATA位点发挥开关作用巧妙编排这些基因的表达变化，保证红系分化按照一定的程序有序进行。因此，GATA因子转换失调势必影响GATA开关的有效开启，进而干扰红系分化。项目拟观察苯代谢物处理的红系祖细胞在诱导红系分化时GATA因子转换是否准确实现，红系分化关键基因的GATA位点能否有效发挥开关作用以调节基因的有序表达或沉默，从而探讨GATA因子转换和GATA开关在苯代谢物抑制红系分化中的作用，以充分认识苯的红系血液毒性机制。

The erythropoietic depression has been widely observed in benzene-exposed human and animal individuals, but little is known about its mechanism. Our precious study has shown that phenolic metabolites of benzene inhibited erythroid differentiation of K562 cells, accompanied by decreased expression of erythroid specific transcription factors GATA2 and GATA1, and reduced GATA1 occupany of GATA motifs in globin gene loci. During erythroid differentiation, GATA1 and GATA2 show dynamic changes in their expression profiles, and the dominant GATA factor switched from GATA2 to GATA1, which is referred to as the “GATA Factor Switching”. The GATA Factor Switching leads to changes in the occupancy of GATA motifs in regulatory regions of erythroid genes from GATA2 to GATA1, and GATA motifs as a switch (GATA-Switch) control their expression. Undoubtedly, disturbed GATA Factor Switching will lead to abnormal erythroid differentiation. In present project, it is to be addressed whether GATA Factor Switching occurs, and GATA motifs in erythroid genes function as switchs to control erythroid differentiation in benzene metabolites-exposed erythroid progenitors when the progenitors are treated with erythroid differentiation inducer, which will provide evidence to elucidate the underlying mechanism of erythroid toxicity of benzene.