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Analysis of the thrombopoietin receptor (MPL) promoter implicates GATA and
Ets proteins in the coregulation of megakaryocyte-specific genes
S Deveaux, A Filipe, V Lemarchandel, J Ghysdael, PH Romeo and V Mignotte
INSERM U. 91, Hopital Henri Mondor, Creteil, France.
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.
Volume 87,
Issue 11,
pp. 4678-4685,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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