Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues

We tested whether sterol-regulatory element binding proteins (SREBPs) mediate sterol-regulated transactivation of the Niemann-Pick C-1 (NPC-1) gene. Loading granulosa cells with 22- or 25-hydroxycholesterol decreased NPC-1 mRNA, whereas culturing in cholesterol-depleted medium or inhibition of chole...
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Autor*in:	Nicolas Gévry [verfasserIn] Kristina Schoonjans [verfasserIn] Fréderic Guay [verfasserIn] Bruce D. Murphy [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2008

Schlagwörter:	sterol regulatory element binding protein gene transcription cholesterol trafficking granulosa cells

Übergeordnetes Werk:	In: Journal of Lipid Research - Elsevier, 2021, 49(2008), 5, Seite 1024-1033
Übergeordnetes Werk:	volume:49 ; year:2008 ; number:5 ; pages:1024-1033

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1194/jlr.M700554-JLR200

Katalog-ID:	DOAJ055477372

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520			\|a We tested whether sterol-regulatory element binding proteins (SREBPs) mediate sterol-regulated transactivation of the Niemann-Pick C-1 (NPC-1) gene. Loading granulosa cells with 22- or 25-hydroxycholesterol decreased NPC-1 mRNA, whereas culturing in cholesterol-depleted medium or inhibition of cholesterol biosynthesis increased NPC-1 promoter activity and NPC-1 mRNA abundance. Cotransfection of SREBP1a, SREBP1c, and SREBP2 and the NPC-1 promoter-luciferase reporter into granulosa cell lines increased the transcriptional activity of porcine, human, and mouse NPC-1 promoters. Deletion analysis of the 5′ flanking region of the pig NPC-1 gene demonstrated significant promoter activity between fragments −934 and −636 bp upstream from the transcription initiation site. Sequence analysis revealed three sterol-regulatory elements (SREs) clustered between −558 and −650 bp. Each site, along with E-box sequences, bound recombinant SREBP in electromobility shift assays. Mutation of all three sites attenuated the SREBP induction of promoter activity. Chromatin immunoprecipitation (ChIP) assays revealed that cholesterol depletion enriched the association of both SREBP and acetylated histone H3 with the NPC-1 promoter fragment containing the three SREs. ChIP analysis confirmed that SREBP's association with SRE and the E-box was enriched in cells cultured in cholesterol-depleted medium. We conclude that NPC-1 is sterol-regulated, achieved by SREBP acting via SRE and the E-box sequences.
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spelling	10.1194/jlr.M700554-JLR200 doi (DE-627)DOAJ055477372 (DE-599)DOAJc4067974c6d94f38a596e4ac87b5e34a DE-627 ger DE-627 rakwb eng QD415-436 Nicolas Gévry verfasserin aut Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We tested whether sterol-regulatory element binding proteins (SREBPs) mediate sterol-regulated transactivation of the Niemann-Pick C-1 (NPC-1) gene. Loading granulosa cells with 22- or 25-hydroxycholesterol decreased NPC-1 mRNA, whereas culturing in cholesterol-depleted medium or inhibition of cholesterol biosynthesis increased NPC-1 promoter activity and NPC-1 mRNA abundance. Cotransfection of SREBP1a, SREBP1c, and SREBP2 and the NPC-1 promoter-luciferase reporter into granulosa cell lines increased the transcriptional activity of porcine, human, and mouse NPC-1 promoters. Deletion analysis of the 5′ flanking region of the pig NPC-1 gene demonstrated significant promoter activity between fragments −934 and −636 bp upstream from the transcription initiation site. Sequence analysis revealed three sterol-regulatory elements (SREs) clustered between −558 and −650 bp. Each site, along with E-box sequences, bound recombinant SREBP in electromobility shift assays. Mutation of all three sites attenuated the SREBP induction of promoter activity. Chromatin immunoprecipitation (ChIP) assays revealed that cholesterol depletion enriched the association of both SREBP and acetylated histone H3 with the NPC-1 promoter fragment containing the three SREs. ChIP analysis confirmed that SREBP's association with SRE and the E-box was enriched in cells cultured in cholesterol-depleted medium. We conclude that NPC-1 is sterol-regulated, achieved by SREBP acting via SRE and the E-box sequences. sterol regulatory element binding protein gene transcription cholesterol trafficking granulosa cells Biochemistry Kristina Schoonjans verfasserin aut Fréderic Guay verfasserin aut Bruce D. Murphy verfasserin aut In Journal of Lipid Research Elsevier, 2021 49(2008), 5, Seite 1024-1033 (DE-627)26601593X (DE-600)1466675-3 15397262 nnns volume:49 year:2008 number:5 pages:1024-1033 https://doi.org/10.1194/jlr.M700554-JLR200 kostenfrei https://doaj.org/article/c4067974c6d94f38a596e4ac87b5e34a kostenfrei http://www.sciencedirect.com/science/article/pii/S0022227520425891 kostenfrei https://doaj.org/toc/0022-2275 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 49 2008 5 1024-1033
allfields_unstemmed	10.1194/jlr.M700554-JLR200 doi (DE-627)DOAJ055477372 (DE-599)DOAJc4067974c6d94f38a596e4ac87b5e34a DE-627 ger DE-627 rakwb eng QD415-436 Nicolas Gévry verfasserin aut Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We tested whether sterol-regulatory element binding proteins (SREBPs) mediate sterol-regulated transactivation of the Niemann-Pick C-1 (NPC-1) gene. Loading granulosa cells with 22- or 25-hydroxycholesterol decreased NPC-1 mRNA, whereas culturing in cholesterol-depleted medium or inhibition of cholesterol biosynthesis increased NPC-1 promoter activity and NPC-1 mRNA abundance. Cotransfection of SREBP1a, SREBP1c, and SREBP2 and the NPC-1 promoter-luciferase reporter into granulosa cell lines increased the transcriptional activity of porcine, human, and mouse NPC-1 promoters. Deletion analysis of the 5′ flanking region of the pig NPC-1 gene demonstrated significant promoter activity between fragments −934 and −636 bp upstream from the transcription initiation site. Sequence analysis revealed three sterol-regulatory elements (SREs) clustered between −558 and −650 bp. Each site, along with E-box sequences, bound recombinant SREBP in electromobility shift assays. Mutation of all three sites attenuated the SREBP induction of promoter activity. Chromatin immunoprecipitation (ChIP) assays revealed that cholesterol depletion enriched the association of both SREBP and acetylated histone H3 with the NPC-1 promoter fragment containing the three SREs. ChIP analysis confirmed that SREBP's association with SRE and the E-box was enriched in cells cultured in cholesterol-depleted medium. We conclude that NPC-1 is sterol-regulated, achieved by SREBP acting via SRE and the E-box sequences. sterol regulatory element binding protein gene transcription cholesterol trafficking granulosa cells Biochemistry Kristina Schoonjans verfasserin aut Fréderic Guay verfasserin aut Bruce D. Murphy verfasserin aut In Journal of Lipid Research Elsevier, 2021 49(2008), 5, Seite 1024-1033 (DE-627)26601593X (DE-600)1466675-3 15397262 nnns volume:49 year:2008 number:5 pages:1024-1033 https://doi.org/10.1194/jlr.M700554-JLR200 kostenfrei https://doaj.org/article/c4067974c6d94f38a596e4ac87b5e34a kostenfrei http://www.sciencedirect.com/science/article/pii/S0022227520425891 kostenfrei https://doaj.org/toc/0022-2275 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 49 2008 5 1024-1033
allfieldsGer	10.1194/jlr.M700554-JLR200 doi (DE-627)DOAJ055477372 (DE-599)DOAJc4067974c6d94f38a596e4ac87b5e34a DE-627 ger DE-627 rakwb eng QD415-436 Nicolas Gévry verfasserin aut Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We tested whether sterol-regulatory element binding proteins (SREBPs) mediate sterol-regulated transactivation of the Niemann-Pick C-1 (NPC-1) gene. Loading granulosa cells with 22- or 25-hydroxycholesterol decreased NPC-1 mRNA, whereas culturing in cholesterol-depleted medium or inhibition of cholesterol biosynthesis increased NPC-1 promoter activity and NPC-1 mRNA abundance. Cotransfection of SREBP1a, SREBP1c, and SREBP2 and the NPC-1 promoter-luciferase reporter into granulosa cell lines increased the transcriptional activity of porcine, human, and mouse NPC-1 promoters. Deletion analysis of the 5′ flanking region of the pig NPC-1 gene demonstrated significant promoter activity between fragments −934 and −636 bp upstream from the transcription initiation site. Sequence analysis revealed three sterol-regulatory elements (SREs) clustered between −558 and −650 bp. Each site, along with E-box sequences, bound recombinant SREBP in electromobility shift assays. Mutation of all three sites attenuated the SREBP induction of promoter activity. Chromatin immunoprecipitation (ChIP) assays revealed that cholesterol depletion enriched the association of both SREBP and acetylated histone H3 with the NPC-1 promoter fragment containing the three SREs. ChIP analysis confirmed that SREBP's association with SRE and the E-box was enriched in cells cultured in cholesterol-depleted medium. We conclude that NPC-1 is sterol-regulated, achieved by SREBP acting via SRE and the E-box sequences. sterol regulatory element binding protein gene transcription cholesterol trafficking granulosa cells Biochemistry Kristina Schoonjans verfasserin aut Fréderic Guay verfasserin aut Bruce D. Murphy verfasserin aut In Journal of Lipid Research Elsevier, 2021 49(2008), 5, Seite 1024-1033 (DE-627)26601593X (DE-600)1466675-3 15397262 nnns volume:49 year:2008 number:5 pages:1024-1033 https://doi.org/10.1194/jlr.M700554-JLR200 kostenfrei https://doaj.org/article/c4067974c6d94f38a596e4ac87b5e34a kostenfrei http://www.sciencedirect.com/science/article/pii/S0022227520425891 kostenfrei https://doaj.org/toc/0022-2275 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 49 2008 5 1024-1033
allfieldsSound	10.1194/jlr.M700554-JLR200 doi (DE-627)DOAJ055477372 (DE-599)DOAJc4067974c6d94f38a596e4ac87b5e34a DE-627 ger DE-627 rakwb eng QD415-436 Nicolas Gévry verfasserin aut Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We tested whether sterol-regulatory element binding proteins (SREBPs) mediate sterol-regulated transactivation of the Niemann-Pick C-1 (NPC-1) gene. Loading granulosa cells with 22- or 25-hydroxycholesterol decreased NPC-1 mRNA, whereas culturing in cholesterol-depleted medium or inhibition of cholesterol biosynthesis increased NPC-1 promoter activity and NPC-1 mRNA abundance. Cotransfection of SREBP1a, SREBP1c, and SREBP2 and the NPC-1 promoter-luciferase reporter into granulosa cell lines increased the transcriptional activity of porcine, human, and mouse NPC-1 promoters. Deletion analysis of the 5′ flanking region of the pig NPC-1 gene demonstrated significant promoter activity between fragments −934 and −636 bp upstream from the transcription initiation site. Sequence analysis revealed three sterol-regulatory elements (SREs) clustered between −558 and −650 bp. Each site, along with E-box sequences, bound recombinant SREBP in electromobility shift assays. Mutation of all three sites attenuated the SREBP induction of promoter activity. Chromatin immunoprecipitation (ChIP) assays revealed that cholesterol depletion enriched the association of both SREBP and acetylated histone H3 with the NPC-1 promoter fragment containing the three SREs. ChIP analysis confirmed that SREBP's association with SRE and the E-box was enriched in cells cultured in cholesterol-depleted medium. We conclude that NPC-1 is sterol-regulated, achieved by SREBP acting via SRE and the E-box sequences. sterol regulatory element binding protein gene transcription cholesterol trafficking granulosa cells Biochemistry Kristina Schoonjans verfasserin aut Fréderic Guay verfasserin aut Bruce D. Murphy verfasserin aut In Journal of Lipid Research Elsevier, 2021 49(2008), 5, Seite 1024-1033 (DE-627)26601593X (DE-600)1466675-3 15397262 nnns volume:49 year:2008 number:5 pages:1024-1033 https://doi.org/10.1194/jlr.M700554-JLR200 kostenfrei https://doaj.org/article/c4067974c6d94f38a596e4ac87b5e34a kostenfrei http://www.sciencedirect.com/science/article/pii/S0022227520425891 kostenfrei https://doaj.org/toc/0022-2275 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 49 2008 5 1024-1033
language	English
source	In Journal of Lipid Research 49(2008), 5, Seite 1024-1033 volume:49 year:2008 number:5 pages:1024-1033
sourceStr	In Journal of Lipid Research 49(2008), 5, Seite 1024-1033 volume:49 year:2008 number:5 pages:1024-1033
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	sterol regulatory element binding protein gene transcription cholesterol trafficking granulosa cells Biochemistry
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container_title	Journal of Lipid Research
authorswithroles_txt_mv	Nicolas Gévry @@aut@@ Kristina Schoonjans @@aut@@ Fréderic Guay @@aut@@ Bruce D. Murphy @@aut@@
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callnumber-first	Q - Science
author	Nicolas Gévry
spellingShingle	Nicolas Gévry misc QD415-436 misc sterol regulatory element binding protein misc gene transcription misc cholesterol trafficking misc granulosa cells misc Biochemistry Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues
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topic_title	QD415-436 Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues sterol regulatory element binding protein gene transcription cholesterol trafficking granulosa cells
topic	misc QD415-436 misc sterol regulatory element binding protein misc gene transcription misc cholesterol trafficking misc granulosa cells misc Biochemistry
topic_unstemmed	misc QD415-436 misc sterol regulatory element binding protein misc gene transcription misc cholesterol trafficking misc granulosa cells misc Biochemistry
topic_browse	misc QD415-436 misc sterol regulatory element binding protein misc gene transcription misc cholesterol trafficking misc granulosa cells misc Biochemistry
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues
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title_full	Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues
author_sort	Nicolas Gévry
journal	Journal of Lipid Research
journalStr	Journal of Lipid Research
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author_browse	Nicolas Gévry Kristina Schoonjans Fréderic Guay Bruce D. Murphy
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author-letter	Nicolas Gévry
doi_str_mv	10.1194/jlr.M700554-JLR200
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title_sort	cholesterol supply and srebps modulate transcription of the niemann-pick c-1 gene in steroidogenic tissues
callnumber	QD415-436
title_auth	Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues
abstract	We tested whether sterol-regulatory element binding proteins (SREBPs) mediate sterol-regulated transactivation of the Niemann-Pick C-1 (NPC-1) gene. Loading granulosa cells with 22- or 25-hydroxycholesterol decreased NPC-1 mRNA, whereas culturing in cholesterol-depleted medium or inhibition of cholesterol biosynthesis increased NPC-1 promoter activity and NPC-1 mRNA abundance. Cotransfection of SREBP1a, SREBP1c, and SREBP2 and the NPC-1 promoter-luciferase reporter into granulosa cell lines increased the transcriptional activity of porcine, human, and mouse NPC-1 promoters. Deletion analysis of the 5′ flanking region of the pig NPC-1 gene demonstrated significant promoter activity between fragments −934 and −636 bp upstream from the transcription initiation site. Sequence analysis revealed three sterol-regulatory elements (SREs) clustered between −558 and −650 bp. Each site, along with E-box sequences, bound recombinant SREBP in electromobility shift assays. Mutation of all three sites attenuated the SREBP induction of promoter activity. Chromatin immunoprecipitation (ChIP) assays revealed that cholesterol depletion enriched the association of both SREBP and acetylated histone H3 with the NPC-1 promoter fragment containing the three SREs. ChIP analysis confirmed that SREBP's association with SRE and the E-box was enriched in cells cultured in cholesterol-depleted medium. We conclude that NPC-1 is sterol-regulated, achieved by SREBP acting via SRE and the E-box sequences.
abstractGer	We tested whether sterol-regulatory element binding proteins (SREBPs) mediate sterol-regulated transactivation of the Niemann-Pick C-1 (NPC-1) gene. Loading granulosa cells with 22- or 25-hydroxycholesterol decreased NPC-1 mRNA, whereas culturing in cholesterol-depleted medium or inhibition of cholesterol biosynthesis increased NPC-1 promoter activity and NPC-1 mRNA abundance. Cotransfection of SREBP1a, SREBP1c, and SREBP2 and the NPC-1 promoter-luciferase reporter into granulosa cell lines increased the transcriptional activity of porcine, human, and mouse NPC-1 promoters. Deletion analysis of the 5′ flanking region of the pig NPC-1 gene demonstrated significant promoter activity between fragments −934 and −636 bp upstream from the transcription initiation site. Sequence analysis revealed three sterol-regulatory elements (SREs) clustered between −558 and −650 bp. Each site, along with E-box sequences, bound recombinant SREBP in electromobility shift assays. Mutation of all three sites attenuated the SREBP induction of promoter activity. Chromatin immunoprecipitation (ChIP) assays revealed that cholesterol depletion enriched the association of both SREBP and acetylated histone H3 with the NPC-1 promoter fragment containing the three SREs. ChIP analysis confirmed that SREBP's association with SRE and the E-box was enriched in cells cultured in cholesterol-depleted medium. We conclude that NPC-1 is sterol-regulated, achieved by SREBP acting via SRE and the E-box sequences.
abstract_unstemmed	We tested whether sterol-regulatory element binding proteins (SREBPs) mediate sterol-regulated transactivation of the Niemann-Pick C-1 (NPC-1) gene. Loading granulosa cells with 22- or 25-hydroxycholesterol decreased NPC-1 mRNA, whereas culturing in cholesterol-depleted medium or inhibition of cholesterol biosynthesis increased NPC-1 promoter activity and NPC-1 mRNA abundance. Cotransfection of SREBP1a, SREBP1c, and SREBP2 and the NPC-1 promoter-luciferase reporter into granulosa cell lines increased the transcriptional activity of porcine, human, and mouse NPC-1 promoters. Deletion analysis of the 5′ flanking region of the pig NPC-1 gene demonstrated significant promoter activity between fragments −934 and −636 bp upstream from the transcription initiation site. Sequence analysis revealed three sterol-regulatory elements (SREs) clustered between −558 and −650 bp. Each site, along with E-box sequences, bound recombinant SREBP in electromobility shift assays. Mutation of all three sites attenuated the SREBP induction of promoter activity. Chromatin immunoprecipitation (ChIP) assays revealed that cholesterol depletion enriched the association of both SREBP and acetylated histone H3 with the NPC-1 promoter fragment containing the three SREs. ChIP analysis confirmed that SREBP's association with SRE and the E-box was enriched in cells cultured in cholesterol-depleted medium. We conclude that NPC-1 is sterol-regulated, achieved by SREBP acting via SRE and the E-box sequences.
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title_short	Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues
url	https://doi.org/10.1194/jlr.M700554-JLR200 https://doaj.org/article/c4067974c6d94f38a596e4ac87b5e34a http://www.sciencedirect.com/science/article/pii/S0022227520425891 https://doaj.org/toc/0022-2275
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author2	Kristina Schoonjans Fréderic Guay Bruce D. Murphy
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doi_str	10.1194/jlr.M700554-JLR200
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up_date	2024-07-03T15:12:28.916Z
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Cholesterol supply and SREBPs modulate transcription of the Niemann-Pick C-1 gene in steroidogenic tissues

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