|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3366-3380
Functional Characterization of the Human Platelet Glycoprotein V Gene
Promoter: A Specific Marker of Late Megakaryocytic Differentiation
Adeline Lepage,
Georges Uzan,
Nadège Touche,
Martine Morales,
Jean-Pierre Cazenave,
François Lanza, and
Corinne de
la Salle
From INSERM U. 311, Etablissement de Transfusion Sanguine de
Strasbourg, Strasbourg, France; and INSERM U. 506, Hôpital Paul
Brousse, Villejuif, France.
Glycoprotein V (GPV), a subunit of the platelet GPIb-V-IX receptor
for von Willebrand factor and thrombin, is specifically found in
platelets and mature megakaryocytes. Studies of the GPV gene can
therefore provide insight into the mechanisms governing megakaryocyte
differentiation. The human GPV promoter was isolated, and elements
important for its tissue specific transcriptional activity were
localized using systematic DNase I protection and reporter deletion
assays. A  1413/+25 fragment inserted into a luciferase reporter
construct displayed promoter activity in Dami and HEL but not in K562,
HL60, or HeLa cells. Progressive 5' to 3' deletion showed a
putative enhancer region in the 1413/903 segment that contained
closely spaced GATA and Ets sites protected from DNase I digestion in
Dami extracts. Regions similar to a GPIIb gene repressor were found at
816 and 610, with the first exhibiting repressor activity in Dami
and HEL cells and the second protected from DNAse I. Deletions from
362 to 103, an area containing protected sites for Sp1, STAT, and
GATA, induced a progressive decrease in activity. The 103/+1
fragment, bearing a proximal Ets footprinted site and a GATA/Ets tandem
footprint, displayed 75% activity relative to the full-length promoter
and retained cell specificity. In summary, this work defines several
regions of the GPV gene promoter important for its activity. It
contains megakaryocyte-specific signals, including
erythro-megakaryocytic GATA, and Ets cis-acting elements, GPIIb-like
repressor domains, and binding sites for ubiquitous factors such as
Sp1, ETF, and STAT.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. Ohneda, S. Ohmori, Y. Ishijima, M. Nakano, and M. Yamamoto
Characterization of a Functional ZBP-89 Binding Site That Mediates Gata1 Gene Expression during Hematopoietic Development
J. Biol. Chem.,
October 30, 2009;
284(44):
30187 - 30199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Oettgen
Regulation of Vascular Inflammation and Remodeling by ETS Factors
Circ. Res.,
November 24, 2006;
99(11):
1159 - 1166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Hazony, J. Lu, C. St. Hilaire, and K. Ravid
Hematopoietic gene promoters subjected to a group-combinatorial study of DNA samples: identification of a megakaryocytic selective DNA signature
Nucleic Acids Res.,
September 11, 2006;
34(16):
4416 - 4428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Jackers, G. Szalai, O. Moussa, and D. K. Watson
Ets-dependent Regulation of Target Gene Expression during Megakaryopoiesis
J. Biol. Chem.,
December 10, 2004;
279(50):
52183 - 52190.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lu, M. J. Pazin, and K. Ravid
Properties of Ets-1 Binding to Chromatin and Its Effect on Platelet Factor 4 Gene Expression
Mol. Cell. Biol.,
January 1, 2004;
24(1):
428 - 441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Okada, R. Nagai, T. Sato, E. Matsuura, T. Minami, I. Morita, and T. Doi
Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene
Blood,
June 15, 2003;
101(12):
4748 - 4756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Holmes, N. Bartle, M. Eisbacher, and B. H. Chong
Cloning and Analysis of the Thrombopoietin-induced Megakaryocyte-specific Glycoprotein VI Promoter and Its Regulation by GATA-1, Fli-1, and Sp1
J. Biol. Chem.,
December 6, 2002;
277(50):
48333 - 48341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Kunzelmann-Marche, J.-M. Freyssinet, and M. C. Martinez
Loss of Plasma Membrane Phospholipid Asymmetry Requires Raft Integrity. ROLE OF TRANSIENT RECEPTOR POTENTIAL CHANNELS AND ERK PATHWAY
J. Biol. Chem.,
May 24, 2002;
277(22):
19876 - 19881.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. F. Mao, V. R. Vaidyula, S. P. Kunapuli, and A. K. Rao
Lineage-specific defect in gene expression in human platelet phospholipase C-beta 2 deficiency
Blood,
February 1, 2002;
99(3):
905 - 911.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Lepage, M. Leboeuf, J.-P. Cazenave, C. de la Salle, F. Lanza, and G. Uzan
The alpha IIbbeta 3 integrin and GPIb-V-IX complex identify distinct stages in the maturation of CD34+ cord blood cells to megakaryocytes
Blood,
December 15, 2000;
96(13):
4169 - 4177.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jandrot-Perrus, S. Busfield, A.-H. Lagrue, X. Xiong, N. Debili, T. Chickering, J.-P. L. Couedic, A. Goodearl, B. Dussault, C. Fraser, et al.
Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily
Blood,
September 1, 2000;
96(5):
1798 - 1807.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-H. Lagrue-Lak-Hal, N. Debili, G. Kingbury, C. Lecut, J.-P. Le Couedic, J.-L. Villeval, M. Jandrot-Perrus, and W. Vainchenker
Expression and Function of the Collagen Receptor GPVI during Megakaryocyte Maturation
J. Biol. Chem.,
April 27, 2001;
276(18):
15316 - 15325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
