|
J Biol Chem, Vol. 273, Issue 28, 17810-17816, July 10, 1998
Transactivation of the Human Apolipoprotein CII Promoter by
Orphan and Ligand-dependent Nuclear Receptors
THE REGULATORY ELEMENT CIIC IS A THYROID HORMONE RESPONSE
ELEMENT
Dimitris
Kardassis,
Eftichia
Sacharidou, and
Vassilis I.
Zannis
From the Division of Basic Sciences, Section of Biochemistry,
Department Of Medicine, University Of Crete and Institute Of Molecular
Biology and Biotechnology, Heraklion, Crete, Greece
The regulatory elements CIIC
( 159/ 116) and CIIB ( 102/ 81) of the apolipoprotein CII (apoCII)
promoter have distinct specificities for orphan nuclear receptors
(Vorgia, P., Zannis, V. I., and Kardassis, D. (1998) J. Biol. Chem. 273, 4188-4199). In this communication we
investigated the contribution of ligand-dependent and
orphan nuclear receptors on the transcriptional regulation of the human apoCII gene. It was found that element CIIC in
addition to ARP-1 and EAR-2 binds RXR /T3R heterodimers strongly,
whereas element CIIB binds hepatic nuclear factor 4 (HNF-4)
exclusively. Binding is abolished by mutations that alter the HRE
binding motifs.
Transient cotransfection experiments showed that in the presence of T3,
RXR /T3R heterodimers transactivated the 205/+18 apoCII promoter
1.6- and 11-fold in HepG2 and COS-1 respectively. No transactivation
was observed in the presence of 9-cis-retinoic acid.
Transactivation requires the regulatory element CIIC, suggesting that
this element contains a thyroid hormone response element. HNF-4 did not
affect the apoCII promoter activity in HepG2 cells. However, mutations
in the HNF-4 binding site on element CIIB and inhibition of HNF-4
synthesis in HepG2 cells by antisense HNF-4 constructs decreased the
apoCII promoter activity to 25-40% of the control, indicating that
HNF-4 is a positive regulator of the apoCII gene. ARP-1 repressed the
205/+18 but not the 104/+18 apoCII promoter activity in HepG2
cells, indicating that the repression depends on the regulatory element
CIIC. In contrast, combination of ARP-1 and HNF-4 transactivated
different apoCII promoter segments as well as a minimal adenovirus
major late promoter driven by the regulatory element CIIB. Mutagenesis
or deletion of elements CIIB or CIIC established that the observed
transactivation requires DNA binding of one of the two factors and may
result from HNF-4-ARP-1 interactions that elicit the transactivation
functions of HNF-4.
The combined data indicate that RXR /T3R in the presence of T3 and
HNF-4 can upregulate the apoCII promoter activity by binding to the
regulatory elements CIIC and CIIB, respectively. In addition, ARP-1 can
either have inhibitory or stimulatory effects on the apoCII promoter
activity via different mechanisms.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
L. E. Rufibach, S. A. Duncan, M. Battle, and S. S. Deeb
Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter
J. Lipid Res.,
July 1, 2006;
47(7):
1463 - 1477.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Rhee, H. Ge, W. Yang, M. Fan, C. Handschin, M. Cooper, J. Lin, C. Li, and B. M. Spiegelman
Partnership of PGC-1{alpha} and HNF4{alpha} in the Regulation of Lipoprotein Metabolism
J. Biol. Chem.,
May 26, 2006;
281(21):
14683 - 14690.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Prieur, T. Huby, H. Coste, F. G. Schaap, M. J. Chapman, and J. C. Rodriguez
Thyroid Hormone Regulates the Hypotriglyceridemic Gene APOA5
J. Biol. Chem.,
July 29, 2005;
280(30):
27533 - 27543.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Anisfeld, H. R. Kast-Woelbern, H. Lee, Y. Zhang, F. Y. Lee, and P. A. Edwards
Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling
J. Lipid Res.,
March 1, 2005;
46(3):
458 - 468.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Aggelidou, P. Iordanidou, P. Tsantili, G. Papadopoulos, and M. Hadzopoulou-Cladaras
Critical Role of Residues Defining the Ligand Binding Pocket in Hepatocyte Nuclear Factor-4{alpha}
J. Biol. Chem.,
July 16, 2004;
279(29):
30680 - 30688.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Duda, Y.-I. Chi, and S. E. Shoelson
Structural Basis for HNF-4{alpha} Activation by Ligand and Coactivator Binding
J. Biol. Chem.,
May 28, 2004;
279(22):
23311 - 23316.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Kim, S. Xie, S.-D. Yeh, Y.-F. Lee, L. L. Collins, Y.-C. Hu, C.-R. Shyr, X.-M. Mu, N.-C. Liu, Y.-T. Chen, et al.
Disruption of TR4 Orphan Nuclear Receptor Reduces the Expression of Liver Apolipoprotein E/C-I/C-II Gene Cluster
J. Biol. Chem.,
November 21, 2003;
278(47):
46919 - 46926.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Inoue, G. P. Hayhurst, J. Inoue, M. Mori, and F. J. Gonzalez
Defective Ureagenesis in Mice Carrying a Liver-specific Disruption of Hepatocyte Nuclear Factor 4alpha (HNF4alpha ). HNF4alpha REGULATES ORNITHINE TRANSCARBAMYLASE IN VIVO
J. Biol. Chem.,
July 5, 2002;
277(28):
25257 - 25265.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. P. Hayhurst, Y.-H. Lee, G. Lambert, J. M. Ward, and F. J. Gonzalez
Hepatocyte Nuclear Factor 4{alpha} (Nuclear Receptor 2A1) Is Essential for Maintenance of Hepatic Gene Expression and Lipid Homeostasis
Mol. Cell. Biol.,
February 15, 2001;
21(4):
1393 - 1403.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
J. Li, G. Ning, and S. A. Duncan
Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha
Genes & Dev.,
February 15, 2000;
14(4):
464 - 474.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
H. Dell and M. Hadzopoulou-Cladaras
CREB-binding Protein Is a Transcriptional Coactivator for Hepatocyte Nuclear Factor-4 and Enhances Apolipoprotein Gene Expression
J. Biol. Chem.,
March 26, 1999;
274(13):
9013 - 9021.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Kardassis, K. Pardali, and V. I. Zannis
SMAD Proteins Transactivate the Human ApoCIII Promoter by Interacting Physically and Functionally with Hepatocyte Nuclear Factor 4
J. Biol. Chem.,
December 22, 2000;
275(52):
41405 - 41414.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|