Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (1091K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Castillo-Olivares, A. d.
Right arrow Articles by Gil, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Castillo-Olivares, A. d.
Right arrow Articles by Gil, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2000, Vol. 28, No. 18 3587-3593
© 2000 Oxford University Press

Role of FXR and FTF in bile acid-mediated suppression of cholesterol 7{alpha}-hydroxylase transcription

Antonio del Castillo-Olivares and Gregorio Gil*

Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, PO Box 980614, Richmond, VA 23298-0614, USA

Bile acid biosynthesis is subjected to feedback regulation whereby bile acids down-regulate their own synthesis. The major point of this regulation is at the level of cholesterol 7{alpha}-hydroxylase (7{alpha}-hydroxylase), which controls bile acid output from the classic pathway. This regulation is at the level of transcription of the gene. Two bile acid response elements have been localized within the 5'-flanking region of the rat gene and these elements overlap three nuclear receptor binding sites for hepatocyte nuclear factor (HNF-4), liver X receptor (LXR) and {alpha}1-fetoprotein transcription factor (FTF). Recently it has been shown that bile acids are physiological ligands for the farnesyl X receptor (FXR), which suggested that FXR could function by binding to one of the three nuclear receptor sites to mediate regulation of 7{alpha}-hydroxylase transcription by bile acids. In this study we show that FXR is indeed a crucial factor for bile acid-mediated regulation, but that it functions without binding to DNA. Furthermore, we also demonstrate that neither the LXR nor the HNF-4 sites are involved in bile acid-mediated regulation of 7{alpha}-hydroxylase transcription. Most importantly, we show that the FTF site is essential for regulation of 7{alpha}-hydroxylase by bile acids, similar to what we have recently demonstrated for another gene of the bile acid biosynthetic pathway, the sterol 12{alpha}-hydroxylase gene. These studies demonstrate the crucial role of FTF in the expression and regulation of a critical gene in the bile acid biosynthetic pathways.

* To whom correspondence should be addressed. Tel: +1 804 828 0140; Fax: +1 804 828 0676; Email: ggil@vcu.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
D.-J. Shin and T. F. Osborne
FGF15/FGFR4 Integrates Growth Factor Signaling with Hepatic Bile Acid Metabolism and Insulin Action
J. Biol. Chem., April 24, 2009; 284(17): 11110 - 11120.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
P. Lefebvre, B. Cariou, F. Lien, F. Kuipers, and B. Staels
Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Physiol Rev, January 1, 2009; 89(1): 147 - 191.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
Y. Ma, L. Xu, D. Rodriguez-Agudo, X. Li, D. M. Heuman, P. B. Hylemon, W. M. Pandak, and S. Ren
25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway
Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1369 - E1379.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
Y.-K. Lee, D. R. Schmidt, C. L. Cummins, M. Choi, L. Peng, Y. Zhang, B. Goodwin, R. E. Hammer, D. J. Mangelsdorf, and S. A. Kliewer
Liver Receptor Homolog-1 Regulates Bile Acid Homeostasis but Is Not Essential for Feedback Regulation of Bile Acid Synthesis
Mol. Endocrinol., June 1, 2008; 22(6): 1345 - 1356.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
X. Song, R. Kaimal, B. Yan, and R. Deng
Liver receptor homolog 1 transcriptionally regulates human bile salt export pump expression
J. Lipid Res., May 1, 2008; 49(5): 973 - 984.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Xu, O. L. Tavares-Sanchez, Q. Li, J. Fernando, C. M. Rodriguez, E. J. Studer, W. M. Pandak, P. B. Hylemon, and G. Gil
Activation of Bile Acid Biosynthesis by the p38 Mitogen-activated Protein Kinase (MAPK): HEPATOCYTE NUCLEAR FACTOR-4{alpha} PHOSPHORYLATION BY THE p38 MAPK IS REQUIRED FOR CHOLESTEROL 7{alpha}-HYDROXYLASE EXPRESSION
J. Biol. Chem., August 24, 2007; 282(34): 24607 - 24614.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Yu, F. Wang, C. Jin, X. Huang, and W. L. McKeehan
Independent Repression of Bile Acid Synthesis and Activation of c-Jun N-terminal Kinase (JNK) by Activated Hepatocyte Fibroblast Growth Factor Receptor 4 (FGFR4) and Bile Acids
J. Biol. Chem., May 6, 2005; 280(18): 17707 - 17714.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. K. Kemper, H. Kim, J. Miao, S. Bhalla, and Y. Bae
Role of an mSin3A-Swi/Snf Chromatin Remodeling Complex in the Feedback Repression of Bile Acid Biosynthesis by SHP
Mol. Cell. Biol., September 1, 2004; 24(17): 7707 - 7719.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-F. Pare, D. Malenfant, C. Courtemanche, M. Jacob-Wagner, S. Roy, D. Allard, and L. Belanger
The Fetoprotein Transcription Factor (FTF) Gene Is Essential to Embryogenesis and Cholesterol Homeostasis and Is Regulated by a DR4 Element
J. Biol. Chem., May 14, 2004; 279(20): 21206 - 21216.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. del Castillo-Olivares, J. A. Campos, W. M. Pandak, and G. Gil
The Role of {alpha}1-Fetoprotein Transcription Factor/LRH-1 in Bile Acid Biosynthesis: A KNOWN NUCLEAR RECEPTOR ACTIVATOR THAT CAN ACT AS A SUPPRESSOR OF BILE ACID BIOSYNTHESIS
J. Biol. Chem., April 16, 2004; 279(16): 16813 - 16821.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D.-J. Shin, J. A. Campos, G. Gil, and T. F. Osborne
PGC-1{alpha} Activates CYP7A1 and Bile Acid Biosynthesis
J. Biol. Chem., December 12, 2003; 278(50): 50047 - 50052.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. De Fabiani, N. Mitro, F. Gilardi, D. Caruso, G. Galli, and M. Crestani
Coordinated Control of Cholesterol Catabolism to Bile Acids and of Gluconeogenesis via a Novel Mechanism of Transcription Regulation Linked to the Fasted-to-fed Cycle
J. Biol. Chem., October 3, 2003; 278(40): 39124 - 39132.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Fayard, K. Schoonjans, J.-S. Annicotte, and J. Auwerx
Liver Receptor Homolog 1 Controls the Expression of Carboxyl Ester Lipase
J. Biol. Chem., September 12, 2003; 278(37): 35725 - 35731.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
R O. Elferink
Cholestasis
Gut, May 1, 2003; 52(90002): ii42 - 48.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
M.-C. Gerbod-Giannone, A. del Castillo-Olivares, S. Janciauskiene, G. Gil, and P. B Hylemon
Suppression of Cholesterol 7alpha -Hydroxylase Transcription and Bile Acid Synthesis by an alpha 1-Antitrypsin Peptide via Interaction with alpha 1-Fetoprotein Transcription Factor
J. Biol. Chem., November 1, 2002; 277(45): 42973 - 42980.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
B. Goodwin and S. A. Kliewer
Nuclear Receptors: I. Nuclear receptors and bile acid homeostasis
Am J Physiol Gastrointest Liver Physiol, June 1, 2002; 282(6): G926 - G931.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. del Castillo-Olivares and G. Gil
Differential Effects of Sterol Regulatory Binding Proteins 1 and 2 on Sterol 12alpha -Hydroxylase. SREBP-2 SUPPRESSES THE STEROL 12alpha -HYDROXYLASE PROMOTER
J. Biol. Chem., February 15, 2002; 277(8): 6750 - 6757.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
P. A. Edwards, H. R. Kast, and A. M. Anisfeld
BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis
J. Lipid Res., January 1, 2002; 43(1): 2 - 12.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Inokuchi, E. Hinoshita, Y. Iwamoto, K. Kohno, M. Kuwano, and T. Uchiumi
Enhanced Expression of the Human Multidrug Resistance Protein 3 by Bile Salt in Human Enterocytes. A TRANSCRIPTIONAL CONTROL OF A PLAUSIBLE BILE ACID TRANSPORTER
J. Biol. Chem., December 7, 2001; 276(50): 46822 - 46829.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. del Castillo-Olivares and G. Gil
Suppression of sterol 12{alpha}-hydroxylase transcription by the short heterodimer partner: insights into the repression mechanism
Nucleic Acids Res., October 1, 2001; 29(19): 4035 - 4042.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-F. Pare, S. Roy, L. Galarneau, and L. Belanger
The Mouse Fetoprotein Transcription Factor (FTF) Gene Promoter Is Regulated by Three GATA Elements with Tandem E Box and Nkx Motifs, and FTF in Turn Activates the Hnf3beta , Hnf4alpha , and Hnf1alpha Gene Promoters
J. Biol. Chem., April 13, 2001; 276(16): 13136 - 13144.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Gupta, R. T. Stravitz, P. Dent, and P. B. Hylemon
Down-regulation of Cholesterol 7alpha -Hydroxylase (CYP7A1) Gene Expression by Bile Acids in Primary Rat Hepatocytes Is Mediated by the c-Jun N-terminal Kinase Pathway
J. Biol. Chem., May 4, 2001; 276(19): 15816 - 15822.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. De Fabiani, N. Mitro, A. C. Anzulovich, A. Pinelli, G. Galli, and M. Crestani
The Negative Effects of Bile Acids and Tumor Necrosis Factor-alpha on the Transcription of Cholesterol 7alpha -Hydroxylase Gene (CYP7A1) Converge to Hepatic Nuclear Factor-4. A NOVEL MECHANISM OF FEEDBACK REGULATION OF BILE ACID SYNTHESIS MEDIATED BY NUCLEAR RECEPTORS
J. Biol. Chem., August 10, 2001; 276(33): 30708 - 30716.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. C. Hunt, K. Solaas, B. F. Kase, and S. E. H. Alexson
Characterization of an Acyl-CoA Thioesterase That Functions as a Major Regulator of Peroxisomal Lipid Metabolism
J. Biol. Chem., January 4, 2002; 277(2): 1128 - 1138.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. T. Lu, J. J. Repa, and D. J. Mangelsdorf
Orphan Nuclear Receptors as eLiXiRs and FiXeRs of Sterol Metabolism
J. Biol. Chem., October 5, 2001; 276(41): 37735 - 37738.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.