NDLI: Analysis of the thrombopoietin receptor (MPL) promoter implicates GATA and Ets proteins in the coregulation of megakaryocyte-specific genes

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Analysis of the thrombopoietin receptor (MPL) promoter implicates GATA and Ets proteins in the coregulation of megakaryocyte-specific genes

Content Provider	Scilit
Author	Deveaux, S. Filipe, A. Lemarchandel, V. Ghysdael, J. Romeo, Paul-Henri Mignotte, V.
Copyright Year	1996
Description	He 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.
Related Links	https://ashpublications.org/blood/article-pdf/87/11/4678/620162/4678.pdf
Ending Page	4685
Page Count	8
Starting Page	4678
DOI	10.1182/blood.v87.11.4678.bloodjournal87114678
Journal	Blood
Issue Number	11
Volume Number	87
Language	English
Publisher	American Society of Hematology
Publisher Date	1996-06-01
Access Restriction	Open
Subject Keyword	Biochemistry and Molecular Biology Hematology Differentiation Affinity Gata Destruction Thrombopoietin Mpl Megakaryocyte Ets Proteins Journal: Blood (Vol- 116, Issue- 11)
Content Type	Text
Resource Type	Article

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