Schematic representation of the main events leading to impaired fetal erythropoiesis. (A) Gata2 which is expressed in erythroid progenitors, positively regulates Gata1 and its own expression.39 Gata1 also positively regulates its own expression but represses Gata2. Progression in erythroid differentiation becomes possible due to the Gata1/Gata2 switch on the promoter of erythroid genes resulting in their activation. Gata2 repression is an essential step in erythroid differentiation and is executed by several factors including Gata1 and the decline in ERG expression. (B) In the ERG/Gata1s mice, several factors block erythroid differentiation. In the absence of the N-terminal domain of Gata1, Gata1s fails to repress Gata2, erythroid genes are not activated, and differentiation is blocked. Furthermore, the Gata2 repressor Myb is downregulated by ERG and Gata1s. Because Myb functions as a Gata2 repressor, decreased Myb levels result in an increase in Gata2 expression. In the ERG transgenic model, the ERG expression level fails to decline with erythroid differentiation, thus further maintaining Gata2 expression and preventing erythroid cells to fully differentiate to erythrocytes.
