HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gauthier, B. Articles by McPherson, R. Search for Related Content PubMed PubMed Citation Articles by Gauthier, B. Articles by McPherson, R. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 40, 1284-1293, July 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

Characterization of a cholesterol response element (CRE) in the promoter of the cholesteryl ester transfer protein gene: functional role of the transcription factors SREBP-1a, -2, and YY1.

Correspondence to: Ruth McPherson

Cholesteryl ester transfer protein (CETP) is expressed in human adipocytes, where it acts to promote selective uptake of HDL-CE (Benoist, F., M. McDonnell, P. Lau, R. Milne, and R. McPherson. 1997. J. Biol. Chem. 272: 23572;–23577). In contrast to other major sterol-responsive genes such as 3-hydroxy-3-methylglutaryl coenzyme A reductase CETP expression is up-regulated rather than down-regulated in response to cholesterol. To define elements involved in cholesterol-mediated up-regulation of CETP gene expression, deletion derivatives of the CETP promoter were cloned into a luciferase reporter construct and transfected into the human liposarcoma cell line SW872, cultured in the presence or absence of lipoproteins. A fragment associated with a positive cholesterol response was identified between nucleotides -361 and -138 (relative to the initiation site of transcription) of the promoter. This region contains a tandem repeat of a sequence known to mediate sterol dependent regulation of the hamster HMG-CoA reductase gene. We have putatively denoted this region, the cholesterol response element (CRE).

Using gel mobility shift assays we demonstrate that both YY1 and SREBP-1 interact with the CRE of CETP. Furthermore, in transient co-transfection experiments, both YY1 and SREBP-1a were found to trans-activate, in a dose-dependent manner, the luciferase activity of constructs harboring the CRE. We also demonstrate that SREBP-2, is able to trans-activate a luciferase construct harboring the CRE although much less effectively as compared to SREBP-1. Finally, functional analysis of the CRE confirms its regulatory role in modulating CETP gene expression through its interaction with YY1 and SREBP-1a.—Gauthier, B., M. Robb, F. Gaudet, G. S. Ginsburg, and R. McPherson. Characterization of a cholesterol response element (CRE) in the promoter of the cholesteryl ester transfer protein gene: functional role of the transcription factors SREBP-1a, -2, and YY1. J. Lipid Res. 1999. 40: 1284;–1293.

Supplementary key words: gene expression, liposarcoma cells, sterol regulatory element, lipid transfer protein, reverse cholesterol transport

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. S. MacLean, S. Vadlamudi, K. G. MacDonald, W. J. Pories, and H. A. Barakat Suppression of Hepatic Cholesteryl Ester Transfer Protein Expression in Obese Humans with the Development of Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2250 - 2258. [Abstract] [Full Text] [PDF]

				T. Brun, I. Franklin, L. St-Onge, A. Biason-Lauber, E. J. Schoenle, C. B. Wollheim, and B. R. Gauthier The diabetes-linked transcription factor PAX4 promotes {beta}-cell proliferation and survival in rat and human islets J. Cell Biol., December 20, 2004; 167(6): 1123 - 1135. [Abstract] [Full Text] [PDF]

				W. Le Goff, M. Guerin, L. Petit, M. J. Chapman, and J. Thillet Regulation of human CETP gene expression: role of SP1 and SP3 transcription factors at promoter sites -690, -629, and -37 J. Lipid Res., July 1, 2003; 44(7): 1322 - 1331. [Abstract] [Full Text] [PDF]

				W. Le Goff, M. Guerin, M. J. Chapman, and J. Thillet A CYP7A promoter binding factor site and Alu repeat in the distal promoter region are implicated in regulation of human CETP gene expression J. Lipid Res., May 1, 2003; 44(5): 902 - 910. [Abstract] [Full Text] [PDF]

				F. V. van Venrooij, R. P. Stolk, J.-D. Banga, T. P. Sijmonsma, A. van Tol, D. W. Erkelens, and G. M. Dallinga-Thie Common Cholesteryl Ester Transfer Protein Gene Polymorphisms and the Effect of Atorvastatin Therapy in Type 2 Diabetes Diabetes Care, April 1, 2003; 26(4): 1216 - 1223. [Abstract] [Full Text] [PDF]

				A. Gauthier, G. Vassiliou, F. Benoist, and R. McPherson Adipocyte Low Density Lipoprotein Receptor-related Protein Gene Expression and Function Is Regulated by Peroxisome Proliferator-activated Receptor gamma J. Biol. Chem., March 28, 2003; 278(14): 11945 - 11953. [Abstract] [Full Text] [PDF]

				A. H.E.M. Klerkx, M. W.T. Tanck, J. J.P. Kastelein, H. O.F. Molhuizen, J. W. Jukema, A. H. Zwinderman, and J. A. Kuivenhoven Haplotype analysis of the CETP gene: not TaqIB, but the closely linked -629C->A polymorphism and a novel promoter variant are independently associated with CETP concentration Hum. Mol. Genet., January 15, 2003; 12(2): 111 - 123. [Abstract] [Full Text] [PDF]

				Y. J. Jiang, G. M. Hatch, D. Mymin, T. Dembinski, E. A. Kroeger, and P. C. Choy Modulation of cytosolic phospholipase A2 by PPAR activators in human preadipocytes J. Lipid Res., May 1, 2001; 42(5): 716 - 724. [Abstract] [Full Text]

				L. K. Christenson, T. F. Osborne, J. M. McAllister, and J. F. Strauss III Conditional Response of the Human Steroidogenic Acute Regulatory Protein Gene Promoter to Sterol Regulatory Element Binding Protein-1a Endocrinology, January 1, 2001; 142(1): 28 - 36. [Abstract] [Full Text] [PDF]

				A. von Eckardstein, J.-R. Nofer, and G. Assmann High Density Lipoproteins and Arteriosclerosis : Role of Cholesterol Efflux and Reverse Cholesterol Transport Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 13 - 27. [Abstract] [Full Text] [PDF]

				S. Santamarina-Fojo, K. Peterson, C. Knapper, Y. Qiu, L. Freeman, J.-F. Cheng, J. Osorio, A. Remaley, X.-P. Yang, C. Haudenschild, et al. Complete genomic sequence of the human ABCA1 gene: Analysis of the human and mouse ATP-binding cassette A promoter PNAS, July 5, 2000; 97(14): 7987 - 7992. [Abstract] [Full Text] [PDF]