Analysis of the MPL promoter revealed that GATA-1 and Ets proteins bind to specific motifs and additively trans-activate megakaryocyte-specific gene expression.
GATA-1 and Ets proteins coregulate the megakaryocyte-specific expression of the thrombopoietin receptor (MPL) gene.
The MPL gene codes for the thrombopoietin receptor, whose ligand specifically controls megakaryocytic differentiation. To understand the molecular basis for the megakaryocyte-specific expression of MPL, we analyzed the promoter of this gene. A 200 bp fragment is sufficient for high-level specific expression. This fragment can bind several trans-acting factors in vitro, including GATA-1 and members of the Ets family. GATA-1 binds with low affinity to a unique GATA motif at -70 in the MPL promoter, and destruction of this site yields only a modest decrease in expression level in HEL cells. Ets proteins also bind with low affinity to two sites. One is located at position -15 and its destruction reduces expression to 50%; the other is located immediately downstream of the GATA motif and plays a crucial role in expression of the promoter in HEL cells, as its inactivation reduces expression to 15%. Furthermore, GATA-1 and two Ets proteins, Ets-1 and Fli-1, can trans-activate the MPL promoter in heterologous cells. The effects of GATA-1 and these two Ets proteins are additive. Together with our previous results on the glycoprotein IIb (GpIIb) promoter, this study indicates a molecular basis for the coregulation of early markers of megakaryocyte differentiation.
DeVeaux et al. (Sat,) conducted a other in Megakaryocyte differentiation. Analysis of the MPL promoter revealed that GATA-1 and Ets proteins bind to specific motifs and additively trans-activate megakaryocyte-specific gene expression.