Recent reports indicate that apolipoprotein (apo) A-II, the second most abundant protein of high-density lipoproteins, plays a crucial role in counteracting the beneficial effect of apo A-I against atherogenesis. Transcription of the human apo A-II gene is controlled by an enhancer comprising 14 regulatory elements located upstream of its promoter whereas the first intron of this gene behaves as a silencer. Here we show that two sequence elements account for the repressive activity of this intron and correspond to negative regulatory elements termed NRE I and NRE II. The activity of intron I and the nuclear proteins binding to NRE I and II are encountered in hepatic cells but not in non-hepatic cells studied here. Both NREs form nucleoprotein complexes of very similar physicochemical characteristics and bind the same or closely related proteins. Site-directed mutagenesis, transient transfection and gel-shift analysis experiments indicate that both NREs exhibit similar structures, being composed of two sites required for maximal activity and optimal binding of transcription factors. Therefore two negative regulatory elements of similar structure and function, placed in tandem, account for the repressive activity of the first intron of the human apo A-II gene. These NREs do not exhibit structural similarity with known NREs of other genes.
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September 1996
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Research Article|
September 01 1996
Two regulatory elements of similar structure and placed in tandem account for the repressive activity of the first intron of the human apolipoprotein A-II gene
Jean-Pierre BOSSU;
Jean-Pierre BOSSU
1U. 325 INSERM, Département d'Athérosclérose, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59000 Lille, France
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François L. CHARTIER;
François L. CHARTIER
1U. 325 INSERM, Département d'Athérosclérose, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59000 Lille, France
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Jean-Charles FRUCHART;
Jean-Charles FRUCHART
1U. 325 INSERM, Département d'Athérosclérose, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59000 Lille, France
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Johan AUWERX;
Johan AUWERX
1U. 325 INSERM, Département d'Athérosclérose, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59000 Lille, France
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Bart STAELS;
Bart STAELS
1U. 325 INSERM, Département d'Athérosclérose, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59000 Lille, France
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Bernard LAINE
Bernard LAINE
*
*To whom correspondence should be addressed. Present address: Laboratoire de Biochimie Structurale, C. J. F. INSERM 9203, Faculté de Médecine, 1 Place de Verdun, 59 045 Lille, France.
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Publisher: Portland Press Ltd
Received:
September 18 1995
Revision Received:
March 29 1996
Accepted:
April 30 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 318 (2): 547–553.
Article history
Received:
September 18 1995
Revision Received:
March 29 1996
Accepted:
April 30 1996
Citation
Jean-Pierre BOSSU, François L. CHARTIER, Jean-Charles FRUCHART, Johan AUWERX, Bart STAELS, Bernard LAINE; Two regulatory elements of similar structure and placed in tandem account for the repressive activity of the first intron of the human apolipoprotein A-II gene. Biochem J 1 September 1996; 318 (2): 547–553. doi: https://doi.org/10.1042/bj3180547
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