DNA binding and mutagenesis in vitro established that the −67/−55 region of the apoA-II (apolipoprotein A-II) promoter contains a thyroid HRE (hormone response element), which strongly binds RXRα (retinoid X receptor α)/T3Rβ (thyroid receptor β) heterodimers and weakly T3Rβ homodimers, but does not bind other homo- or heterodimers of RXRα or orphan nuclear receptors. Transactivation was abolished by point mutations in the thyroid HRE. In co-transfection experiments of HEK-293 (human embryonic kidney 293) cells, the −911/+29 human apoA-II promoter was transactivated strongly by RXRα/T3Rβ heterodimers in the presence of RA (9-cis retinoic acid) or T3 (tri-iodothyronine). Homopolymeric promoters containing either three copies of the −73/−40 (element AIIAB) or four copies of the −738/−712 (element AIIJ) apoA-II promoter could be transactivated by RXRα/T3Rβ heterodimers in COS-7 cells only in the presence of T3 or RA respectively. RXRα/T3Rβ heterodimers and USF2a (upstream stimulatory factor 2a) synergistically transactivated the −911/+29 apoA-II promoter in the presence of T3. USF2a also enhanced the activity of a GAL4–T3Rβ fusion protein in the presence of T3 and suppressed the activity of a GAL4–RXRα fusion protein in the presence of RA. These findings suggest a functional specificity of the two HREs of the apoA-II promoter for retinoids and thyroids, which is modulated by synergistic or antagonistic interactions between RXRα/T3Rβ heterodimers and the ubiquitous transcription factor USF2a.
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December 2003
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Research Article|
December 01 2003
Functional specificity of two hormone response elements present on the human apoA-II promoter that bind retinoid X receptor α/thyroid receptor β heterodimers for retinoids and thyroids: synergistic interactions between thyroid receptor β and upstream stimulatory factor 2a
Eudoxia HATZIVASSILIOU;
Eudoxia HATZIVASSILIOU
1
*Biomedical Sciences Research Center Al. Fleming, Institute of Immunology, 14-16 Al. Fleming Str., Vari GR-16672, Greece
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George KOUKOS;
George KOUKOS
1
†Department of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology of Hellas, Herakleion GR-71110, Greece
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Agnes RIBEIRO;
Agnes RIBEIRO
‡Institut National de la Santé et de la Recherche Médicale U505, Universite Pierre et Marie Curie, Institut des Cordeliers, 15 rue de l'Ecole de Medecine, 75006 Paris, France
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Vassilis ZANNIS;
Vassilis ZANNIS
†Department of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology of Hellas, Herakleion GR-71110, Greece
§Section of Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street CABR-W509, Boston, MA 02118, U.S.A.
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Dimitris KARDASSIS
Dimitris KARDASSIS
2
†Department of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology of Hellas, Herakleion GR-71110, Greece
2To whom correspondence should be addressed (e-mail kardasis@imbb.forth.gr).
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Publisher: Portland Press Ltd
Received:
April 10 2003
Revision Received:
August 05 2003
Accepted:
September 05 2003
Accepted Manuscript online:
September 05 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 376 (2): 423–431.
Article history
Received:
April 10 2003
Revision Received:
August 05 2003
Accepted:
September 05 2003
Accepted Manuscript online:
September 05 2003
Citation
Eudoxia HATZIVASSILIOU, George KOUKOS, Agnes RIBEIRO, Vassilis ZANNIS, Dimitris KARDASSIS; Functional specificity of two hormone response elements present on the human apoA-II promoter that bind retinoid X receptor α/thyroid receptor β heterodimers for retinoids and thyroids: synergistic interactions between thyroid receptor β and upstream stimulatory factor 2a. Biochem J 1 December 2003; 376 (2): 423–431. doi: https://doi.org/10.1042/bj20030549
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