Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoter

Apolipoprotein CIII (apoCIII) plays an important role in plasma triglyceride and remnant lipoprotein metabolism. Because hypertriglyceridemia is an independent risk factor in coronary artery disease and the presence in plasma of triglyceride-rich remnant lipoproteins is correlated with atheroscleros...

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Authors: Coste, Hervé, Rodríguez Rubio, Joan Carles
Format: article
Status:Published version
Publication Date:2002
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/105711
Online Access:https://hdl.handle.net/2445/105711
Access Level:Open access
Keyword:Apoproteïnes
Triglicèrids
Aterosclerosi
Receptors nuclears (Bioquímica)
Apolipoproteins
Triglycerides
Atherosclerosis
Nuclear receptors (Biochemistry)
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spelling Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoterCoste, HervéRodríguez Rubio, Joan CarlesApoproteïnesTriglicèridsAterosclerosiReceptors nuclears (Bioquímica)ApolipoproteinsTriglyceridesAtherosclerosisNuclear receptors (Biochemistry)Apolipoprotein CIII (apoCIII) plays an important role in plasma triglyceride and remnant lipoprotein metabolism. Because hypertriglyceridemia is an independent risk factor in coronary artery disease and the presence in plasma of triglyceride-rich remnant lipoproteins is correlated with atherosclerosis, considerable research efforts have been focused on the identification of factors regulating apoCIII gene expression to decrease its production. Here we report that the orphan nuclear hormone receptor Rev-erb regulates the human apoCIII gene promoter. In apoCIII expressing human hepatic HepG2 cells, transfection of Rev-erb specifically repressed apoCIII gene promoter activity. We determined by deletion and sitedirected mutagenesis experiments that Rev-erb dependent repression is mainly due to an element present in the proximal promoter of the apoCIII gene. In contrast, we found no functional Rev-erb response elements in the convergently transcribed human apoAI gene or the common regulatory enhancer. The identified Rev-erb response element coincides with a ROR 1 element, and in the present study we provide evidence that functional cross-talk between these orphan receptors modulates the apoCIII promoter. In vitro binding analysis showed that monomers of Rev-erb bound this element but not another upstream ROR 1 response element. In addition, we showed that the closely related nuclear orphan receptor RVR also specifically repressed the human apoCIII gene. These studies underscore a novel physiological role for members of the Rev-erb family of nuclear receptors in the regulation of genes involved in triglyceride metabolism and the pathogenesis of atherosclerosis.American Society for Biochemistry and Molecular Biology2002info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/105711Articles publicats en revistes (Bioquímica i Fisiologia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1074/jbc.M203421200Journal of Biological Chemistry, 2002, vol. 277, num. 30, p. 27120-27129https://doi.org/10.1074/jbc.M203421200(c) American Society for Biochemistry and Molecular Biology, 2002info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1057112026-05-27T06:46:51Z
dc.title.none.fl_str_mv Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoter
title Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoter
spellingShingle Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoter
Coste, Hervé
Apoproteïnes
Triglicèrids
Aterosclerosi
Receptors nuclears (Bioquímica)
Apolipoproteins
Triglycerides
Atherosclerosis
Nuclear receptors (Biochemistry)
title_short Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoter
title_full Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoter
title_fullStr Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoter
title_full_unstemmed Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoter
title_sort Orphan nuclear hormone receptor Rev-erb alpha regulates the human apolipoprotein CIII promoter
dc.creator.none.fl_str_mv Coste, Hervé
Rodríguez Rubio, Joan Carles
author Coste, Hervé
author_facet Coste, Hervé
Rodríguez Rubio, Joan Carles
author_role author
author2 Rodríguez Rubio, Joan Carles
author2_role author
dc.subject.none.fl_str_mv Apoproteïnes
Triglicèrids
Aterosclerosi
Receptors nuclears (Bioquímica)
Apolipoproteins
Triglycerides
Atherosclerosis
Nuclear receptors (Biochemistry)
topic Apoproteïnes
Triglicèrids
Aterosclerosi
Receptors nuclears (Bioquímica)
Apolipoproteins
Triglycerides
Atherosclerosis
Nuclear receptors (Biochemistry)
description Apolipoprotein CIII (apoCIII) plays an important role in plasma triglyceride and remnant lipoprotein metabolism. Because hypertriglyceridemia is an independent risk factor in coronary artery disease and the presence in plasma of triglyceride-rich remnant lipoproteins is correlated with atherosclerosis, considerable research efforts have been focused on the identification of factors regulating apoCIII gene expression to decrease its production. Here we report that the orphan nuclear hormone receptor Rev-erb regulates the human apoCIII gene promoter. In apoCIII expressing human hepatic HepG2 cells, transfection of Rev-erb specifically repressed apoCIII gene promoter activity. We determined by deletion and sitedirected mutagenesis experiments that Rev-erb dependent repression is mainly due to an element present in the proximal promoter of the apoCIII gene. In contrast, we found no functional Rev-erb response elements in the convergently transcribed human apoAI gene or the common regulatory enhancer. The identified Rev-erb response element coincides with a ROR 1 element, and in the present study we provide evidence that functional cross-talk between these orphan receptors modulates the apoCIII promoter. In vitro binding analysis showed that monomers of Rev-erb bound this element but not another upstream ROR 1 response element. In addition, we showed that the closely related nuclear orphan receptor RVR also specifically repressed the human apoCIII gene. These studies underscore a novel physiological role for members of the Rev-erb family of nuclear receptors in the regulation of genes involved in triglyceride metabolism and the pathogenesis of atherosclerosis.
publishDate 2002
dc.date.none.fl_str_mv 2002
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/105711
url https://hdl.handle.net/2445/105711
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1074/jbc.M203421200
Journal of Biological Chemistry, 2002, vol. 277, num. 30, p. 27120-27129
https://doi.org/10.1074/jbc.M203421200
dc.rights.none.fl_str_mv (c) American Society for Biochemistry and Molecular Biology, 2002
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Biochemistry and Molecular Biology, 2002
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Fisiologia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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