STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages.

Apolipoprotein CII (apoCII) is a specific activator of lipoprotein lipase and plays an important role in triglyceride metabolism. The aim of our work was to elucidate the regulatory mechanisms involved in apoCII gene modulation in macrophages. Using Chromosome Conformation Capture we demonstrated th...

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Autores principales:	Violeta G Trusca, Irina C Florea, Dimitris Kardassis, Anca V Gafencu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/40be11683d2b402baab1975896869a5d
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spelling	oai:doaj.org-article:40be11683d2b402baab1975896869a5d2021-11-18T07:12:41ZSTAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages.1932-620310.1371/journal.pone.0040463https://doaj.org/article/40be11683d2b402baab1975896869a5d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22808166/?tool=EBIhttps://doaj.org/toc/1932-6203Apolipoprotein CII (apoCII) is a specific activator of lipoprotein lipase and plays an important role in triglyceride metabolism. The aim of our work was to elucidate the regulatory mechanisms involved in apoCII gene modulation in macrophages. Using Chromosome Conformation Capture we demonstrated that multienhancer 2 (ME.2) physically interacts with the apoCII promoter and this interaction facilitates the transcriptional enhancement of the apoCII promoter by the transcription factors bound on ME.2. We revealed that the transcription factor STAT1, previously shown to bind to its specific site on ME.2, is functional for apoCII gene upregulation. We found that siRNA-mediated inhibition of STAT1 gene expression significantly decreased the apoCII levels, while STAT1 overexpression in RAW 264.7 macrophages increased apoCII gene expression. Using transient transfections, DNA pull down and chromatin immunoprecipitation assays, we revealed a novel STAT1 binding site in the -500/-493 region of the apoCII promoter, which mediates apoCII promoter upregulation by STAT1. Interestingly, STAT1 could not exert its upregulatory effect when the RXRα/T3Rβ binding site located on the apoCII promoter was mutated, suggesting physical and functional interactions between these factors. Using GST pull-down and co-immunoprecipitation assays, we demonstrated that STAT1 physically interacts with RXRα. Taken together, these data revealed that STAT1 bound on ME.2 cooperates with RXRα located on apoCII promoter and upregulates apoCII expression only in macrophages, due to the specificity of the long-range interactions between the proximal and distal regulatory elements. Moreover, we showed for the first time that STAT1 and RXRα physically interact to exert their regulatory function.Violeta G TruscaIrina C FloreaDimitris KardassisAnca V GafencuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e40463 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Violeta G Trusca Irina C Florea Dimitris Kardassis Anca V Gafencu STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages.
description	Apolipoprotein CII (apoCII) is a specific activator of lipoprotein lipase and plays an important role in triglyceride metabolism. The aim of our work was to elucidate the regulatory mechanisms involved in apoCII gene modulation in macrophages. Using Chromosome Conformation Capture we demonstrated that multienhancer 2 (ME.2) physically interacts with the apoCII promoter and this interaction facilitates the transcriptional enhancement of the apoCII promoter by the transcription factors bound on ME.2. We revealed that the transcription factor STAT1, previously shown to bind to its specific site on ME.2, is functional for apoCII gene upregulation. We found that siRNA-mediated inhibition of STAT1 gene expression significantly decreased the apoCII levels, while STAT1 overexpression in RAW 264.7 macrophages increased apoCII gene expression. Using transient transfections, DNA pull down and chromatin immunoprecipitation assays, we revealed a novel STAT1 binding site in the -500/-493 region of the apoCII promoter, which mediates apoCII promoter upregulation by STAT1. Interestingly, STAT1 could not exert its upregulatory effect when the RXRα/T3Rβ binding site located on the apoCII promoter was mutated, suggesting physical and functional interactions between these factors. Using GST pull-down and co-immunoprecipitation assays, we demonstrated that STAT1 physically interacts with RXRα. Taken together, these data revealed that STAT1 bound on ME.2 cooperates with RXRα located on apoCII promoter and upregulates apoCII expression only in macrophages, due to the specificity of the long-range interactions between the proximal and distal regulatory elements. Moreover, we showed for the first time that STAT1 and RXRα physically interact to exert their regulatory function.
format	article
author	Violeta G Trusca Irina C Florea Dimitris Kardassis Anca V Gafencu
author_facet	Violeta G Trusca Irina C Florea Dimitris Kardassis Anca V Gafencu
author_sort	Violeta G Trusca
title	STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages.
title_short	STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages.
title_full	STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages.
title_fullStr	STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages.
title_full_unstemmed	STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages.
title_sort	stat1 interacts with rxrα to upregulate apocii gene expression in macrophages.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/40be11683d2b402baab1975896869a5d
work_keys_str_mv	AT violetagtrusca stat1interactswithrxratoupregulateapociigeneexpressioninmacrophages AT irinacflorea stat1interactswithrxratoupregulateapociigeneexpressioninmacrophages AT dimitriskardassis stat1interactswithrxratoupregulateapociigeneexpressioninmacrophages AT ancavgafencu stat1interactswithrxratoupregulateapociigeneexpressioninmacrophages
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STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages.

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