Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.

The ATP-binding cassette (ABC) transporter ABCB1, encoded by the multidrug resistance gene MDR1, is expressed on brain microvascular endothelium and several types of epithelium, but not on endothelia outside the CNS. It is an essential component of the blood-brain barrier. The aim of this study was...

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Autores principales:	Radka Gromnicova, Ignacio Romero, David Male
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ac192d79ba640dbba894d54ba3b0485
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spelling	oai:doaj.org-article:8ac192d79ba640dbba894d54ba3b04852021-11-18T08:10:57ZTranscriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.1932-620310.1371/journal.pone.0048189https://doaj.org/article/8ac192d79ba640dbba894d54ba3b04852012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133566/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The ATP-binding cassette (ABC) transporter ABCB1, encoded by the multidrug resistance gene MDR1, is expressed on brain microvascular endothelium and several types of epithelium, but not on endothelia outside the CNS. It is an essential component of the blood-brain barrier. The aim of this study was to identify cell-specific controls on the transcription of MDR1 in human brain endothelium. Reporter assays identified a region of 500 bp around the transcription start site that was optimally active in brain endothelium. Chromatin immunoprecipitation identified Sp3 and TFIID associated with this region and EMSA (electrophoretic mobility shift assays) confirmed that Sp3 binds preferentially to an Sp-target site (GC-box) on the MDR1 promoter in brain endothelium. This result contrasts with findings in other cell types and with the colon carcinoma line Caco-2, in which Sp1 preferentially associates with the MDR1 promoter. Differences in MDR1 transcriptional control between brain endothelium and Caco-2 could not be explained by the relative abundance of Sp1:Sp3 nor by the ratio of Sp3 variants, because activating variants of Sp3 were present in both cell types. However differential binding of other transcription factors was also detected in two additional upstream regions of the MDR1 promoter. Identification of cell-specific controls on the transcription of MDR1 indicates that it may be possible to modulate multi-drug resistance on tumours, while leaving the blood brain barrier intact.Radka GromnicovaIgnacio RomeroDavid MalePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48189 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Radka Gromnicova Ignacio Romero David Male Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.
description	The ATP-binding cassette (ABC) transporter ABCB1, encoded by the multidrug resistance gene MDR1, is expressed on brain microvascular endothelium and several types of epithelium, but not on endothelia outside the CNS. It is an essential component of the blood-brain barrier. The aim of this study was to identify cell-specific controls on the transcription of MDR1 in human brain endothelium. Reporter assays identified a region of 500 bp around the transcription start site that was optimally active in brain endothelium. Chromatin immunoprecipitation identified Sp3 and TFIID associated with this region and EMSA (electrophoretic mobility shift assays) confirmed that Sp3 binds preferentially to an Sp-target site (GC-box) on the MDR1 promoter in brain endothelium. This result contrasts with findings in other cell types and with the colon carcinoma line Caco-2, in which Sp1 preferentially associates with the MDR1 promoter. Differences in MDR1 transcriptional control between brain endothelium and Caco-2 could not be explained by the relative abundance of Sp1:Sp3 nor by the ratio of Sp3 variants, because activating variants of Sp3 were present in both cell types. However differential binding of other transcription factors was also detected in two additional upstream regions of the MDR1 promoter. Identification of cell-specific controls on the transcription of MDR1 indicates that it may be possible to modulate multi-drug resistance on tumours, while leaving the blood brain barrier intact.
format	article
author	Radka Gromnicova Ignacio Romero David Male
author_facet	Radka Gromnicova Ignacio Romero David Male
author_sort	Radka Gromnicova
title	Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.
title_short	Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.
title_full	Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.
title_fullStr	Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.
title_full_unstemmed	Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.
title_sort	transcriptional control of the multi-drug transporter abcb1 by transcription factor sp3 in different human tissues.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8ac192d79ba640dbba894d54ba3b0485
work_keys_str_mv	AT radkagromnicova transcriptionalcontrolofthemultidrugtransporterabcb1bytranscriptionfactorsp3indifferenthumantissues AT ignacioromero transcriptionalcontrolofthemultidrugtransporterabcb1bytranscriptionfactorsp3indifferenthumantissues AT davidmale transcriptionalcontrolofthemultidrugtransporterabcb1bytranscriptionfactorsp3indifferenthumantissues
_version_	1718422121132064768

Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.

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