| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Factor VIII is a glycoprotein that is essential for blood
coagulation. Although factor VIII mRNA has been detected in a variety
of human tissues, hepatocytes are considered to be the major source of
plasma factor VIII. In this report we demonstrate that the 5`-flanking
region of the factor VIII gene is able to transcribe a luciferase
reporter gene in three human liver-derived cell lines: PLC/PRF/5,
Chang, and HepG2. DNase I footprinting showed the presence of 19
protein binding sites (labeled A to S, proximal to distal) distributed
along the region from nucleotide -1175 to -9 of the factor
VIII promoter (+1 refers to the translation initiation codon,
ATG). Functional analysis of 5` and 3` deletion mutants of the promoter
region in PLC/PRF/5 cells revealed that the region from -279 to
-64, including sites B to D, contains all the necessary elements
for maximal promoter activity. By using electrophoretic mobility shift
assays with nuclear extracts and purified transcription factors, and
antibody supershift assays we were able to characterize four
liver-enriched factors and one ubiquitous transcription factor
interacting with the proximal promoter binding sites (sites A to E):
hepatocyte nuclear factor (HNF) 1 (site A), NF
Volume 270,
Number 20,
Issue of May 19, pp. 11828-11838, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
B (site B),
C/EBP
and C/EBP
(proximal and distal regions of site C, and
site D), and HNF4 (site E). Additionally, mutation of the putative TATA
box GATAAA (positions -201 to -196) to GACCGA resulted in
less than 2-fold decrease in promoter activity, suggesting that the
putative TATA box is not essential for factor VIII promoter activity.
These results significantly contribute to the understanding of the
control of the hepatic transcription of the factor VIII gene.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. R. Viel, D. K. Machiah, D. M. Warren, M. Khachidze, A. Buil, K. Fernstrom, J. C. Souto, J. M. Peralta, T. Smith, J. Blangero, et al. A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels Blood, May 1, 2007; 109(9): 3713 - 3724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Hong, U. S. Varanasi, W. Yang, and T. Leff AMP-activated Protein Kinase Regulates HNF4{alpha} Transcriptional Activity by Inhibiting Dimer Formation and Decreasing Protein Stability J. Biol. Chem., July 18, 2003; 278(30): 27495 - 27501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Schrem, J. Klempnauer, and J. Borlak Liver-Enriched Transcription Factors in Liver Function and Development. Part I: The Hepatocyte Nuclear Factor Network and Liver-Specific Gene Expression Pharmacol. Rev., March 1, 2002; 54(1): 129 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-L. Hung, E. S. Pollak, R. D. Kudaravalli, V. Arruda, K. Chu, and K. A. High Regulation of human coagulation factor X gene expression by GATA-4 and the Sp family of transcription factors Blood, February 15, 2001; 97(4): 946 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Do, J. F. Healey, E. K. Waller, and P. Lollar Expression of Factor VIII by Murine Liver Sinusoidal Endothelial Cells J. Biol. Chem., July 9, 1999; 274(28): 19587 - 19592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Lenting, J. A. van Mourik, and K. Mertens The Life Cycle of Coagulation Factor VIII in View of Its Structure and Function Blood, December 1, 1998; 92(11): 3983 - 3996. [Full Text] [PDF]
|
|
|
|
|
|
A. Ueda and T. Yoshimura Characterization of cis-Acting Elements of the Gene for Macrophage-stimulating Protein from the Human. THE INVOLVEMENT OF POSITIVE AND NEGATIVE REGULATORY ELEMENTS J. Biol. Chem., August 23, 1996; 271(34): 20265 - 20272. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
