J. Lipid Res. Did you know there is a large type edition? Click here.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M400450-JLR200 on June 16, 2005

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M400450-JLR200v1
46/9/1868    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pramfalk, C.
Right arrow Articles by Parini, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pramfalk, C.
Right arrow Articles by Parini, P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of Lipid Research, Vol. 46, 1868-1876, September 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Control of ACAT2 liver expression by HNF1

Camilla Pramfalk*, Matthew A. Davis{dagger}, Mats Eriksson*, Lawrence L. Rudel{dagger} and Paolo Parini1,*

* Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine and Molecular Nutrition Unit, Center for Nutrition and Toxicology, NOVUM, Karolinska Institutet at Karolinska University Hospital in Huddinge, S-141 86 Stockholm, Sweden
{dagger} Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157

Published, JLR Papers in Press, June 16, 2005. DOI 10.1194/jlr.M400450-JLR200

1 To whom correspondence should be addressed. e-mail: paolo.parini{at}cnt.ki.se

in re-

ACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1 and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in most tissues, whereas ACAT2 is localized to enterocytes and hepatocytes. In this report, we elucidate the mechanisms that control the liver-specific expression of the human ACAT2 gene. We identified hepatic nuclear factor 1 (HNF1) as an important liver-specific trans-acting element for the human ACAT2 gene using the human hepatocellular carcinoma cell lines HuH7 and HepG2. Targeted deletion of the HNF1 binding site in the DNA sequence abolished not only the basal promoter function in HepG2 and HuH7 cells but also the induction of the ACAT2 promoter by HNF1. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that the transcription factors HNF1{alpha} and HNF1ß interact with this region in the human ACAT2 gene in vitro and in vivo.

These data indicate that a) the identified HNF1 binding site serves as a positive regulator sequence, b) the binding site is functionally active both in vivo and in vitro, and c) the transcription factors HNF1{alpha} and HNF1ß, which bind to this site, play an important part in the regulation of the human ACAT2 promoter.

Abbreviations: Cdx-2, caudal-related homeodomain protein-2; C/EBP, CCAAT/enhancer binding protein; ChIP, chromatin immunoprecipitation assay; EMSA, electrophoretic mobility shift assay; HNF1, hepatic nuclear factor 1; MODY, maturity-onset diabetes of the young; TESS, transcription element search software

Supplementary key words liver • cholesterol • transcription factor • gene regulation • metabolism • acyl-coenzyme A:cholesterol acyltransferase • hepatic nuclear factor 1


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


This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
P. Parini, U. Gustafsson, M. A. Davis, L. Larsson, C. Einarsson, M. Wilson, M. Rudling, H. Tomoda, S. Omura, S. Sahlin, et al.
Cholesterol Synthesis Inhibition Elicits an Integrated Molecular Response in Human Livers Including Decreased ACAT2
Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1200 - 1206.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
T. Hiroki, S. A. Liebhaber, and N. E. Cooke
An Intronic Locus Control Region Plays an Essential Role in the Establishment of an Autonomous Hepatic Chromatin Domain for the Human Vitamin D-Binding Protein Gene
Mol. Cell. Biol., November 1, 2007; 27(21): 7365 - 7380.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
E. Ikonen
Mechanisms for cellular cholesterol transport: defects and human disease.
Physiol Rev, October 1, 2006; 86(4): 1237 - 1261.
[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 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.