|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 17, 14443-14450, April 26, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Institute for Clinical Chemistry, University of
Regensburg, 93042 Regensburg, Germany, and the § Pharma
Research Center, Bayer AG, Aprather Wey 18a, D-42096 Wuppertal,
Germany
The ATP-binding cassette transporter
A1 (ABCA1) shows a differentiation-, cAMP-, and
sterol-dependent up-regulation in human monocytes. As part
of an ongoing study, we investigated the proximal promoter regions that
are highly conserved between the human and murine ABCA1 genes. Using
reporter gene assays, we show here that a TATA box 24 bp upstream of
the transcription initiation site is essential for promoter activity in
RAW 264.7 and HepG2 cells, whereas further enhancement of
transcriptional activity is mediated by the The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AJ252201.
Identification of Sterol-independent Regulatory Elements in the
Human ATP-binding Cassette Transporter A1 Promoter
ROLE OF Sp1/3, E-BOX BINDING FACTORS, AND AN ONCOSTATIN
M-RESPONSIVE ELEMENT*
,,
175 bp promoter region.
Gel shift assays revealed in vitro binding of Sp1 to a 91
GnC motif as well as binding of Sp1 and Sp3 to a 157 GnC promoter
region. In co-transfection experiments using Drosophila S2
cells, we demonstrate that Sp3 competes with Sp1 for binding to the
157 GnC motif and acts as a repressor. On the other hand,
overexpression of Sp1 increased ABCA1 mRNA expression in HeLa cells
and enhanced cellular cholesterol and phospholipid efflux in RAW 246.7 macrophages. We also show here that the conserved E-box at position
140 binds upstream stimulatory factors 1 and 2 and hepatic nuclear
factor 1
and that mutagenesis of the E-box enhanced
constitutive ABCA1 expression in RAW 264.7 cells, implying a role for
this element in silencing ABCA1 expression. Besides the functional
importance for basal gene expression, we have identified that the core
promoter region (175 to +224) is also responsible for the induction
of ABCA1 by the cytokine oncostatin M, resulting in a rapid increase in
ABCA1 mRNA levels in HepG2 cells. Interestingly, this oncostatin
M-induced expression is not dependent on the currently known sequence
motifs in the ABCA1 promoter. In conclusion, a functional complex of
cis-elements within the proximal human ABCA1 promoter associated with
the transcription factors Sp1/3, upstream stimulatory factors 1 and 2, and hepatic nuclear factor 1 has been characterized, which allows a
subtle tissue-specific regulation of ABCA1 gene expression.
*
This work was supported in part by Bayer AG Grant PO
708/1-1 and Deutsche Forschungsgemeinschaft Grant LA1203/2-1.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
These two authors contributed equally to this work.
¶
To whom correspondence should be addressed:
Universitätsklinikum Regensburg, Institut für Klinische
Chemie und Blutbank, Franz-Josef-Strau
-Allee 11, 93042 Regensburg, Germany. Tel.: 49-941944-6201; Fax: 49-941-944-6202;
E-mail: gerd.schmitz@klinik.uni-regensburg.de.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Talukdar, S. Bhatnagar, S. Dridi, and F. B. Hillgartner Chenodeoxycholic acid suppresses the activation of acetyl-coenzyme A carboxylase-{alpha} gene transcription by the liver X receptor agonist T0-901317 J. Lipid Res., December 1, 2007; 48(12): 2647 - 2663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Weigelt, W. Ernst, Y. Walczak, S. Ebert, T. Loenhardt, M. Klug, M. Rehli, B. H. F. Weber, and T. Langmann Dap12 expression in activated microglia from retinoschisin-deficient retina and its PU.1-dependent promoter regulation J. Leukoc. Biol., December 1, 2007; 82(6): 1564 - 1574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kyriakou, D. E. Pontefract, E. Viturro, C. P. Hodgkinson, R. C. Laxton, N. Bogari, G. Cooper, M. Davies, J. Giblett, I. N.M. Day, et al. Functional polymorphism in ABCA1 influences age of symptom onset in coronary artery disease patients Hum. Mol. Genet., June 15, 2007; 16(12): 1412 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Miller, P. M. Ridker, P. Libby, and D. J. Kwiatkowski Atherosclerosis: The Path From Genomics to Therapeutics J. Am. Coll. Cardiol., April 17, 2007; 49(15): 1589 - 1599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Oram and J. W. Heinecke ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease Physiol Rev, October 1, 2005; 85(4): 1343 - 1372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Kiss, J. Maric, and Y. L. Marcel Lipid efflux in human and mouse macrophagic cells: evidence for differential regulation of phospholipid and cholesterol efflux J. Lipid Res., September 1, 2005; 46(9): 1877 - 1887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tabibiazar, R. A. Wagner, E. A. Ashley, J. Y. King, R. Ferrara, J. M. Spin, D. A. Sanan, B. Narasimhan, R. Tibshirani, P. S. Tsao, et al. Signature patterns of gene expression in mouse atherosclerosis and their correlation to human coronary disease Physiol Genomics, July 14, 2005; 22(2): 213 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zeng, H. Liao, Y. Liu, T.-S. Lee, M. Zhu, X. Wang, M. B. Stemerman, Y. Zhu, and J. Y.-J. Shyy Sterol-responsive Element-binding Protein (SREBP) 2 Down-regulates ATP-binding Cassette Transporter A1 in Vascular Endothelial Cells: A NOVEL ROLE OF SREBP IN REGULATING CHOLESTEROL METABOLISM J. Biol. Chem., November 19, 2004; 279(47): 48801 - 48807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhou, Y. You, A. J. Ryan, and R. K. Mallampalli Upregulation of surfactant synthesis triggers ABCA1-mediated basolateral phospholipid efflux J. Lipid Res., September 1, 2004; 45(9): 1758 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Agassandian, S. N. Mathur, J. Zhou, F. J. Field, and R. K. Mallampalli Oxysterols Trigger ABCA1-Mediated Basolateral Surfactant Efflux Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 227 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Langmann, C. Schumacher, S. G. Morham, C. Honer, S. Heimerl, C. Moehle, and G. Schmitz ZNF202 is inversely regulated with its target genes ABCA1 and apoE during macrophage differentiation and foam cell formation J. Lipid Res., May 1, 2003; 44(5): 968 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Oram HDL Apolipoproteins and ABCA1: Partners in the Removal of Excess Cellular Cholesterol Arterioscler. Thromb. Vasc. Biol., May 1, 2003; 23(5): 720 - 727. [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 |