|
|
 Previous Article | Table of Contents | Next Article 
An Ets/Sp1 interaction in the 5'-flanking region of the megakaryocyte-
specific alpha IIb gene appears to stabilize Sp1 binding and is essential
for expression of this TATA-less gene
KL Block, Y Shou and M Poncz
Department of Pediatrics, University of Pennsylvania School of Medicine,
Philadelphia, USA.
The megakaryocyte-specific integrin, alpha IIb, is the alpha-subunit of the
alpha IIb/beta 3 complex found on the surface of platelets. This complex is
a receptor for fibrinogen and other ligands when platelets are activated.
Because the alpha IIb gene is specifically expressed in megakaryocytes, the
5'-flanking region was studied as a potential model for
megakaryocyte-specific gene expression. Previous studies have defined some
of the important regulatory elements in the 5'-flanking region of this
gene. The present studies focus on the issue of the molecular basis by
which this TATA-less gene is properly transcribed. A GA-rich region
centered 14 bp upstream from the transcriptional start site appears to be a
nonconsensus Sp1-binding site. Binding to this site is of low affinity, but
is markedly improved by interaction with protein(s) binding at an
Ets-consensus site approximately 20 bp further upstream. Mutation of the
Ets site greatly reduces the ability of Sp1 to bind to its site.
Trans-acting nuclear factors binding to and interaction of the proteins at
these two sites have direct effects on the observed promoter activity in
primary megakaryocyte transient expression studies. These studies provide
further evidence of the role of interactions between Ets-like proteins and
Sp1 in transcriptional activation when a TATA box is not present in the
promoter region of a gene. Based on the presented studies and previous
results, a model is proposed for the regulation of expression of the alpha
IIb gene.
Volume 88,
Issue 6,
pp. 2071-2080,
09/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. M. Gannon and B. T. Kinsella
Regulation of the human thromboxane A2 receptor gene by Sp1, Egr1, NF-E2, GATA-1, and Ets-1 in megakaryocytes
J. Lipid Res.,
December 1, 2008;
49(12):
2590 - 2604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Barre, N. Venkatesan, J. Magdalou, P. Netter, S. Fournel-Gigleux, and M. Ouzzine
Evidence of calcium-dependent pathway in the regulation of human {beta}1,3-glucuronosyltransferase-1 (GlcAT-I) gene expression: a key enzyme in proteoglycan synthesis
FASEB J,
August 1, 2006;
20(10):
1692 - 1694.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Lasagna, O. Fantappie, M. Solazzo, L. Morbidelli, S. Marchetti, G. Cipriani, M. Ziche, and R. Mazzanti
Hepatocyte growth factor and inducible nitric oxide synthase are involved in multidrug resistance-induced angiogenesis in hepatocellular carcinoma cell lines.
Cancer Res.,
March 1, 2006;
66(5):
2673 - 2682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. E. Romero, U. Marvi, Z. E. Niman, and D. A. Roth
The vitamin K-dependent {gamma}-glutamyl carboxylase gene contains a TATA-less promoter with a novel upstream regulatory element
Blood,
August 15, 2003;
102(4):
1333 - 1339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gaudreault, P. Carrier, K. Larouche, S. Leclerc, M. Giasson, L. Germain, and S. L. Guerin
Influence of Sp1/Sp3 Expression on Corneal Epithelial Cells Proliferation and Differentiation Properties in Reconstructed Tissues
Invest. Ophthalmol. Vis. Sci.,
April 1, 2003;
44(4):
1447 - 1457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Kavurma, Y. Bobryshev, and L. M. Khachigian
Ets-1 Positively Regulates Fas Ligand Transcription via Cooperative Interactions with Sp1
J. Biol. Chem.,
September 20, 2002;
277(39):
36244 - 36252.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. V. Tsytsykova and A. E. Goldfeld
Inducer-Specific Enhanceosome Formation Controls Tumor Necrosis Factor Alpha Gene Expression in T Lymphocytes
Mol. Cell. Biol.,
April 15, 2002;
22(8):
2620 - 2631.
[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]
|
|
|
|
|
|
|
D. Kita, T. Takino, M. Nakada, T. Takahashi, J. Yamashita, and H. Sato
Expression of Dominant-negative Form of Ets-1 Suppresses Fibronectin-stimulated Cell Adhesion and Migration Through Down-Regulation of Integrin {alpha}5 Expression in U251 Glioma Cell Line
Cancer Res.,
November 1, 2001;
61(21):
7985 - 7991.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-J. Shi, S.-R. Park, P.-H. Kim, and J. Stavnezer
Roles of Ets proteins, NF-{{kappa}}B and nocodazole in regulating induction of transcription of mouse germline Ig {{alpha}} RNA by transforming growth factor-{beta}1
Int. Immunol.,
June 1, 2001;
13(6):
733 - 746.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Liu, X. Zhong, W. Li, M. G. Brattain, and S. S. Banerji
The Role of Sp1 in the Differential Expression of Transforming Growth Factor-beta Receptor Type II in Human Breast Adenocarcinoma MCF-7 Cells
J. Biol. Chem.,
April 14, 2000;
275(16):
12231 - 12236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Arnaud, V. Nicaud, O. Poirier, F. Rendu, M. Alhenc-Gelas, J.-N. Fiessinger, J. Emmerich, and M. Aiach
Protective Effect of a Thrombin Receptor (Protease-Activated Receptor 1) Gene Polymorphism Toward Venous Thromboembolism
Arterioscler Thromb Vasc Biol,
February 1, 2000;
20(2):
585 - 592.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Lepage, G. Uzan, N. Touche, M. Morales, J.-P. Cazenave, F. Lanza, and C. de la Salle
Functional Characterization of the Human Platelet Glycoprotein V Gene Promoter: A Specific Marker of Late Megakaryocytic Differentiation
Blood,
November 15, 1999;
94(10):
3366 - 3380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Wang, Y. Zhang, J. Lu, S. Sun, and K. Ravid
Mpl Ligand Enhances the Transcription of the Cyclin D3 Gene: A Potential Role for Sp1 Transcription Factor
Blood,
June 15, 1999;
93(12):
4208 - 4221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Muller, R. Yang, L. Beck-von-Peccoz, G. Idos, W. Verbeek, and H. P. Koeffler
Cloning of the cyclin A1 Genomic Structure and Characterization of the Promoter Region. GC BOXES ARE ESSENTIAL FOR CELL CYCLE-REGULATED TRANSCRIPTION OF THE cyclin A1 GENE
J. Biol. Chem.,
April 16, 1999;
274(16):
11220 - 11228.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. P. Haines, R. B. Voyle, T. A. Pelton, R. Forrest, and P. D. Rathjen
Complex Conserved Organization of the Mammalian Leukemia Inhibitory Factor Gene: Regulated Expression of Intracellular and Extracellular Cytokines
J. Immunol.,
April 15, 1999;
162(8):
4637 - 4646.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. S. Bastian, B. A. Kwiatkowski, J. Breininger, S. Danner, and G. Roth
Regulation of the Megakaryocytic Glycoprotein IX Promoter by the Oncogenic Ets Transcription Factor Fli-1
Blood,
April 15, 1999;
93(8):
2637 - 2644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kida, M. Souri, M. Yamamoto, H. Saito, and A. Ichinose
Transcriptional Regulation of Cell Type-specific Expression of the TATA-less A Subunit Gene for Human Coagulation Factor XIII
J. Biol. Chem.,
March 5, 1999;
274(10):
6138 - 6147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-J. Lan, R. J. Lye, N. Holic, J. C. Labus, and B. T. Hinton
Involvement of Polyomavirus Enhancer Activator 3 in the Regulation of Expression of Gamma-Glutamyl Transpeptidase Messenger Ribonucleic Acid-IV in the Rat Epididymis
Biol Reprod,
March 1, 1999;
60(3):
664 - 673.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Y. Jin, C. C. Wilhide, C. Dang, L. Li, S.-X. Li, M. Villa-Garcia, and P. F. Bray
Human Integrin beta 3 Gene Expression: Evidence for a Megakaryocytic Cell-Specific cis-Acting Element
Blood,
October 15, 1998;
92(8):
2777 - 2790.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Carew, E. S. Pollak, K. A. High, and K. A. Bauer
Severe Factor VII Deficiency Due to a Mutation Disrupting an Sp1 Binding Site in the Factor VII Promoter
Blood,
September 1, 1998;
92(5):
1639 - 1645.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Rosmarin, M. Luo, D. G. Caprio, J. Shang, and C. P. Simkevich
Sp1 Cooperates with the ets Transcription Factor, GABP, to Activate the CD18 (beta 2 Leukocyte Integrin) Promoter
J. Biol. Chem.,
May 22, 1998;
273(21):
13097 - 13103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gory, J. Dalmon, M.-H. Prandini, T. Kortulewski, Y. de Launoit, and P. Huber
Requirement of a GT Box (Sp1 Site) and Two Ets Binding Sites for Vascular Endothelial Cadherin Gene Transcription
J. Biol. Chem.,
March 20, 1998;
273(12):
6750 - 6755.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Shou, S. Baron, and M. Poncz
An Sp1-binding Silencer Element Is a Critical Negative Regulator of the Megakaryocyte-specific alpha IIb Gene
J. Biol. Chem.,
March 6, 1998;
273(10):
5716 - 5726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yamaguchi, L. I. Zon, S. J. Ackerman, M. Yamamoto, and T. Suda
Forced GATA-1 Expression in the Murine Myeloid Cell Line M1: Induction of c-Mpl Expression and Megakaryocytic/Erythroid Differentiation
Blood,
January 15, 1998;
91(2):
450 - 457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Yang, D. Boffelli, N. Boonmark, K. Schwartz, and R. Lawn
Apolipoprotein(a) Gene Enhancer Resides within a LINE Element
J. Biol. Chem.,
January 9, 1998;
273(2):
891 - 897.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Doubeikovski, G. Uzan, Z. Doubeikovski, M.-H. Prandini, F. Porteu, S. Gisselbrecht, and I. Dusanter-Fourt
Thrombopoietin-induced Expression of the Glycoprotein IIb Gene Involves the Transcription Factor PU.1/Spi-1 in UT7-Mpl Cells
J. Biol. Chem.,
September 26, 1997;
272(39):
24300 - 24307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Larouche, S. Leclerc, C. Salesse, and S. L. Guerin
Expression of the alpha 5 Integrin Subunit Gene Promoter Is Positively Regulated by the Extracellular Matrix Component Fibronectin through the Transcription Factor Sp1 in Corneal Epithelial Cells in Vitro
J. Biol. Chem.,
December 8, 2000;
275(50):
39182 - 39192.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Gaines, J. N. Geiger, G. Knudsen, D. Seshasayee, and D. M. Wojchowski
GATA-1- and FOG-dependent Activation of Megakaryocytic alpha IIB Gene Expression
J. Biol. Chem.,
October 27, 2000;
275(44):
34114 - 34121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-W. Kim, S.-H. Kim, E.-Y. Lee, N. D. Kim, H.-S. Kang, H.-D. Kim, B.-S. Chung, and C.-D. Kang
Extracellular Signal-regulated Kinase/90-kDa Ribosomal S6 Kinase/Nuclear Factor-kappa B Pathway Mediates Phorbol 12-Myristate 13-Acetate-induced Megakaryocytic Differentiation of K562 Cells
J. Biol. Chem.,
April 13, 2001;
276(16):
13186 - 13191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Price, D. R. Greaves, and H. Watkins
Identification of Novel, Functional Genetic Variants in the Human Matrix Metalloproteinase-2 Gene. ROLE OF Sp1 IN ALLELE-SPECIFIC TRANSCRIPTIONAL REGULATION
J. Biol. Chem.,
March 2, 2001;
276(10):
7549 - 7558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. P. Schick, I. Petrushina, K. C. Brodbeck, and P. Castronuevo
Promoter Regulatory Elements and DNase I-hypersensitive Sites Involved in Serglycin Proteoglycan Gene Expression in Human Erythroleukemia, CHRF 288-11, and HL-60 Cells
J. Biol. Chem.,
June 29, 2001;
276(27):
24726 - 24735.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
