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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mehta, K. D. Articles by Kumar, A. Search for Related Content PubMed PubMed Citation Articles by Mehta, K. D. Articles by Kumar, A. Social Bookmarking                      What's this?

Volume 271, Number 52, Issue of December 27, 1996 pp. 33616-33622
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Identification of a Novel cis-Acting Element Participating in Maximal Induction of the Human Low Density Lipoprotein Receptor Gene Transcription in Response to Low Cellular Cholesterol Levels

(Received for publication, August 14, 1996, and in revised form, September 19, 1996)

From the Departments of Biochemistry & Molecular Biology & Medicine, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205

In this paper, we present both in vivo and in vitro evidence for the presence of a novel cis-acting regulatory element that is required for maximal induction of the human low density lipoprotein (LDL) receptor gene following depletion of cellular sterols in HepG2 cells. First, in vivo dimethyl sulfate footprinting of the human LDL receptor promoter before and after transcriptional induction in HepG2 cells revealed protection from 145 to 126, 5-GAGCTTCACGGGTTAAAAAG-3 (referred to as FP1 site). Second, transient transfections of HepG2 cells with promoter luciferase reporter constructs containing the FP1 site resulted in significant enhancement (approximately 375%) of reporter gene expression in response to low levels of sterols compared with parallel plasmid without the FP1 site. In addition, this response was markedly attenuated on nucleotide substitutions within the FP1 site. Third, by electrophoretic mobility shift assays, the FP1 sequence was found to bind protein(s) from HepG2 nuclear extracts in a sequence-specific manner. In vitro binding of the FP1 mutants paralleled the results obtained for their in vivo transcription. On the basis of competition profiles, the FP1-binding factor is different from the known transcription factors binding to the AT-rich CArG and GArC motifs. Furthermore, the FP1-binding protein is not specific to HepG2 cells because nuclear factor(s) with the same specificity was observed in nuclear extracts of non-hepatic HeLa cells. We conclude that transcriptional induction of the LDL receptor gene in response to sterol depletion is mediated, in part, by an highly conserved novel cis-acting element through the binding of specific nuclear protein(s).

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

This article has been cited by other articles:

				W. Huang, S. Batra, S. Korrapati, V. Mishra, and K. D. Mehta Selective Repression of Low-Density Lipoprotein Receptor Expression by SP600125: Coupling of Histone H3-Ser10 Phosphorylation and Sp1 Occupancy Mol. Cell. Biol., February 15, 2006; 26(4): 1307 - 1317. [Abstract] [Full Text] [PDF]

				G. S. Kapoor, C. Golden, B. Atkins, and K. D. Mehta pp90RSK- and protein kinase C-dependent pathway regulates p42/44MAPK-induced LDL receptor transcription in HepG2 cells J. Lipid Res., March 1, 2003; 44(3): 584 - 593. [Abstract] [Full Text] [PDF]

				F. Zhang, T. E. Ahlborn, C. Li, F. B. Kraemer, and J. Liu Identification of Egr1 as the oncostatin M-induced transcription activator that binds to sterol-independent regulatory element of human LDL receptor promoter J. Lipid Res., September 1, 2002; 43(9): 1477 - 1485. [Abstract] [Full Text] [PDF]

				R A Whittall, S Matheus, T Cranston, G J Miller, and S E Humphries The intron 14 2140+5G>A variant in the low density lipoprotein receptor gene has no effect on plasma cholesterol levels J. Med. Genet., September 1, 2002; 39(9): e57 - 57. [Full Text] [PDF]

				K. D. Mehta, A. Radominska-Pandya, G. S. Kapoor, B. Dave, and B. A. Atkins Critical Role of Diacylglycerol- and Phospholipid-Regulated Protein Kinase C{varepsilon} in Induction of Low-Density Lipoprotein Receptor Transcription in Response to Depletion of Cholesterol Mol. Cell. Biol., June 1, 2002; 22(11): 3783 - 3793. [Abstract] [Full Text] [PDF]

				N. Sekar and J. D. Veldhuis Concerted Transcriptional Activation of the Low Density Lipoprotein Receptor Gene by Insulin and Luteinizing Hormone in Cultured Porcine Granulosa-Luteal Cells: Possible Convergence of Protein Kinase A, Phosphatidylinositol 3-Kinase, and Mitogen-Activated Protein Kinase Signaling Pathways Endocrinology, July 1, 2001; 142(7): 2921 - 2928. [Abstract] [Full Text] [PDF]

				R. S. J. Makar, P. E. Lipsky, and J. A. Cuthbert Multiple mechanisms, independent of sterol regulatory element binding proteins, regulate low density lipoprotein gene transcription J. Lipid Res., May 1, 2000; 41(5): 762 - 774. [Abstract] [Full Text]

				P. Dhawan, A. Bell, A. Kumar, C. Golden, and K. D. Mehta Critical role of p42/44MAPK activation in anisomycin and hepatocyte growth factor-induced LDL receptor expression: activation of Raf-1/MEK-1/p42/44MAPK cascade alone is sufficient to induce LDL receptor expression J. Lipid Res., October 1, 1999; 40(10): 1911 - 1919. [Abstract] [Full Text]

				R. P. Singh, P. Dhawan, C. Golden, G. S. Kapoor, and K. D. Mehta One-way Cross-talk between p38MAPK and p42/44MAPK. INHIBITION OF p38MAPK INDUCES LOW DENSITY LIPOPROTEIN RECEPTOR EXPRESSION THROUGH ACTIVATION OF THE p42/44MAPK CASCADE J. Biol. Chem., July 9, 1999; 274(28): 19593 - 19600. [Abstract] [Full Text] [PDF]

				C. Li, F. B. Kraemer, T. E. Ahlborn, and J. Liu Induction of Low Density Lipoprotein Receptor (LDLR) Transcription by Oncostatin M Is Mediated by the Extracellular Signal-regulated Kinase Signaling Pathway and the Repeat 3 Element of the LDLR Promoter J. Biol. Chem., March 5, 1999; 274(10): 6747 - 6753. [Abstract] [Full Text] [PDF]

				A. Kumar, A. Middleton, T. C. Chambers, and K. D. Mehta Differential Roles of Extracellular Signal-regulated Kinase-1/2 and p38MAPK in Interleukin-1beta - and Tumor Necrosis Factor-alpha -induced Low Density Lipoprotein Receptor Expression in HepG2 Cells J. Biol. Chem., June 19, 1998; 273(25): 15742 - 15748. [Abstract] [Full Text] [PDF]