| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304
1 To whom correspondence should be addressed. e-mail: jingwen.liu{at}med.va.gov
Previously, we identified the low density lipoprotein receptor (LDLR) promoter region -17 to -1 as a novel sterol-independent regulatory element (SIRE) that mediates the stimulating effect of oncostatin M (OM). The goal of this study was to identify the OM-induced transcription activator that binds to the SIRE sequence. By conducting a electrophoretic mobility shift assay (EMSA) followed by UV crosslinking and SDS-PAGE, we show that a protein with a molecular mass of 85 kDa was present in the OM-induced SIRE DNA-protein complex. Western blotting and supershift assays reveal that the 85 kDa factor is early growth response gene 1 (Egr1). The interaction of Egr1 with the SIRE sequence was further confirmed in vivo by chromatin immunoprecipitation assays. The functional role of Egr1 in LDLR transcription was assessed by cotransfection of an Egr1 expression vector with an LDLR promoter reporter construct. We show that overexpression of Egr1 significantly increases LDLR promoter activity when cotransfected with CCAAT/enhancer binding protein ß (c/EBPß) or with cAMP-responsive element binding protein (CREB) expression vectors.
Our studies clearly demonstrate that Egr1 is the OM-induced transcription factor that binds to the SIRE sequence of the LDLR promoter and also suggest that Egr1 may have a functional role in OM-induced upregulation of LDLR transcription through interaction with other SIRE binding proteins such as c/EBPß or CREB.
Abbreviations: Ap1, activator protein 1; ATF, activating transcription factor; C/EBP, CCAAT/enhancer binding protein; CRE, cAMP-responsive element; CREB, cAMP-responsive element binding protein; Egr1, early growth response gene 1; EMSA, electrophoretic mobility shift assay; ERK, extracellular signal regulated kinase; LDLR, low density lipoprotein receptor; OM, oncostatin M; SIRE, sterol-independent regulatory element; SRE-1, sterol regulatory element-1; SREBP, SRE-1 binding protein
Supplementary key words cytokines • early growth response gene 1 • gene transcription • transcriptional activation • signal transduction
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Zhou, P. Abidi, A. Kim, W. Chen, T.-T. Huang, F. B. Kraemer, and J. Liu Transcriptional Activation of Hepatic ACSL3 and ACSL5 by Oncostatin M Reduces Hypertriglyceridemia Through Enhanced {beta}-Oxidation Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2198 - 2205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Kong, P. Abidi, F. B. Kraemer, J.-D. Jiang, and J. Liu In vivo activities of cytokine oncostatin M in the regulation of plasma lipid levels J. Lipid Res., June 1, 2005; 46(6): 1163 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Morello, T. W.A. de Bruin, J. I. Rotter, R. E. Pratt, C. J.H. van der Kallen, G. A. Hladik, V. J. Dzau, C.-C. Liew, and Y.-D. I. Chen Differential Gene Expression of Blood-Derived Cell Lines in Familial Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2149 - 2154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Zhang, M. Lin, P. Abidi, G. Thiel, and J. Liu Specific Interaction of Egr1 and c/EBP{beta} Leads to the Transcriptional Activation of the Human Low Density Lipoprotein Receptor Gene J. Biol. Chem., November 7, 2003; 278(45): 44246 - 44254. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
