|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 February 2001, Vol. 97, No. 4, pp. 946-951
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Regulation of human coagulation factor X gene expression by
GATA-4 and the Sp family of transcription factors
Hsiao-Ling Hung,
Eleanor S. Pollak,
Rama D. Kudaravalli,
Valder Arruda,
Kirk Chu, and
Katherine A. High
From the Departments of Pediatrics and Pathology,
University of Pennsylvania and the Children's Hospital of
Philadelphia, Philadelphia, PA.
Serine protease factor Xa plays a critical role in the coagulation
cascade. Zymogen factor X is synthesized and modified in the liver. To
understand the mechanisms governing the liver-specific expression of
factor X, the proximal promoter of human factor X was previously
characterized. Two crucial cis elements at  73 and 128
and their cognate binding proteins, HNF-4 and NF-Y, respectively, were
identified. In this report, studies are extended to 3 additional cis elements within the factor X promoter. Using gel
mobility shift assays, the liver-enriched protein GATA-4 was
identified as the protein binding to the GATA element at 96. GATA-4
transactivates the factor X promoter 28-fold in transient
transfection experiments. It was also determined that the Sp family of
transcription factors binds 2 DNase I-footprinted sites at 165 and
195. Disruption of Sp protein binding at either site reduces the
promoter activity by half. Simultaneous disruption of both sites
reduces the promoter activity 8-fold. This is the first report
indicating the involvement of GATA-4 in the regulation of
clotting factor expression. These observations provide novel insight
into mechanisms by which the vitamin K-dependent coagulation
factors are regulated.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. G. Muntean and J. D. Crispino
Differential requirements for the activation domain and FOG-interaction surface of GATA-1 in megakaryocyte gene expression and development
Blood,
August 15, 2005;
106(4):
1223 - 1231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. K. Divine, L. J. Staloch, H. Haveri, C. M. Jacobsen, D. B. Wilson, M. Heikinheimo, and T. C. Simon
GATA-4, GATA-5, and GATA-6 activate the rat liver fatty acid binding protein gene in concert with HNF-1{alpha}
Am J Physiol Gastrointest Liver Physiol,
November 1, 2004;
287(5):
G1086 - G1099.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Fluck and W. L. Miller
GATA-4 and GATA-6 Modulate Tissue-Specific Transcription of the Human Gene for P450c17 by Direct Interaction with Sp1
Mol. Endocrinol.,
May 1, 2004;
18(5):
1144 - 1157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
