Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene
Autor(a) principal: | |
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Data de Publicação: | 1997 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/11683 |
Resumo: | The vitamin K-dependent matrix Gla protein (MGP) is synthesized in a wide variety of tissues such as lung, heart, kidney, cartilage, and bone, Expression of the MGP gene is regulated by various growth factors, steroid hormones, and the vitamin A metabolite retinoic acid (RA). In this report, we present evidence that RA down-regulates MGP gene expression in different rat and human cell lines via endogenous retinoid receptors [RA receptor (RAR) and retinoid X receptor (RXR)], Repression of the human MGP (hMGP) gene is specifically mediated by ligand-activated RAR and RXR, Deletion analysis led to the identification of a novel negative response element (NRE) within the hMGP promoter, DNA binding studies performed with bacterially expressed RAR/RXR reveal the formation of a specific heterodimer/ NRE complex, Furthermore, electrophoretic mobility-shift assays performed with proteins from RA-treated cells show that endogenous RAR/RXR binds to the NRE. We demonstrate that the NRE contains a CCAAT box and that both RAR/RXR and CCAAT-binding proteins such as c/EBP beta recognize this common regulatory sequence in the hMGP promoter, Our results indicate that RA-mediated repression of the hMGP gene is due to binding of liganded RAR/RXR to a novel negative RA response element. |
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Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein geneThyroid-hormoneMessenger-RnaCo-repressorCellsReceptorsRatTranscriptionExpressionCartilageThe vitamin K-dependent matrix Gla protein (MGP) is synthesized in a wide variety of tissues such as lung, heart, kidney, cartilage, and bone, Expression of the MGP gene is regulated by various growth factors, steroid hormones, and the vitamin A metabolite retinoic acid (RA). In this report, we present evidence that RA down-regulates MGP gene expression in different rat and human cell lines via endogenous retinoid receptors [RA receptor (RAR) and retinoid X receptor (RXR)], Repression of the human MGP (hMGP) gene is specifically mediated by ligand-activated RAR and RXR, Deletion analysis led to the identification of a novel negative response element (NRE) within the hMGP promoter, DNA binding studies performed with bacterially expressed RAR/RXR reveal the formation of a specific heterodimer/ NRE complex, Furthermore, electrophoretic mobility-shift assays performed with proteins from RA-treated cells show that endogenous RAR/RXR binds to the NRE. We demonstrate that the NRE contains a CCAAT box and that both RAR/RXR and CCAAT-binding proteins such as c/EBP beta recognize this common regulatory sequence in the hMGP promoter, Our results indicate that RA-mediated repression of the hMGP gene is due to binding of liganded RAR/RXR to a novel negative RA response element.NIAMS NIH HHS [AR25921]Natl Acad SciencesSapientiaKirfel, JKelter, MCancela, LMPrice, PASchule, R2018-12-07T14:53:47Z19971997-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/11683eng0027-842410.1073/pnas.94.6.2227info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:23:31Zoai:sapientia.ualg.pt:10400.1/11683Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:03:09.167642Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene |
title |
Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene |
spellingShingle |
Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene Kirfel, J Thyroid-hormone Messenger-Rna Co-repressor Cells Receptors Rat Transcription Expression Cartilage |
title_short |
Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene |
title_full |
Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene |
title_fullStr |
Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene |
title_full_unstemmed |
Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene |
title_sort |
Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene |
author |
Kirfel, J |
author_facet |
Kirfel, J Kelter, M Cancela, LM Price, PA Schule, R |
author_role |
author |
author2 |
Kelter, M Cancela, LM Price, PA Schule, R |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Kirfel, J Kelter, M Cancela, LM Price, PA Schule, R |
dc.subject.por.fl_str_mv |
Thyroid-hormone Messenger-Rna Co-repressor Cells Receptors Rat Transcription Expression Cartilage |
topic |
Thyroid-hormone Messenger-Rna Co-repressor Cells Receptors Rat Transcription Expression Cartilage |
description |
The vitamin K-dependent matrix Gla protein (MGP) is synthesized in a wide variety of tissues such as lung, heart, kidney, cartilage, and bone, Expression of the MGP gene is regulated by various growth factors, steroid hormones, and the vitamin A metabolite retinoic acid (RA). In this report, we present evidence that RA down-regulates MGP gene expression in different rat and human cell lines via endogenous retinoid receptors [RA receptor (RAR) and retinoid X receptor (RXR)], Repression of the human MGP (hMGP) gene is specifically mediated by ligand-activated RAR and RXR, Deletion analysis led to the identification of a novel negative response element (NRE) within the hMGP promoter, DNA binding studies performed with bacterially expressed RAR/RXR reveal the formation of a specific heterodimer/ NRE complex, Furthermore, electrophoretic mobility-shift assays performed with proteins from RA-treated cells show that endogenous RAR/RXR binds to the NRE. We demonstrate that the NRE contains a CCAAT box and that both RAR/RXR and CCAAT-binding proteins such as c/EBP beta recognize this common regulatory sequence in the hMGP promoter, Our results indicate that RA-mediated repression of the hMGP gene is due to binding of liganded RAR/RXR to a novel negative RA response element. |
publishDate |
1997 |
dc.date.none.fl_str_mv |
1997 1997-01-01T00:00:00Z 2018-12-07T14:53:47Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/11683 |
url |
http://hdl.handle.net/10400.1/11683 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0027-8424 10.1073/pnas.94.6.2227 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Natl Acad Sciences |
publisher.none.fl_str_mv |
Natl Acad Sciences |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133266081480704 |