A novel hybrid promoter responsive to pathophysiological and pharmacological regulation

The aim of this study was to construct a promoter containing DNA motifs for an endogenous transcription factor associated with inflammation along with motifs for pharmacological regulation factors. We demonstrate in transfected cells that expression of a gene of interest is induced by hypoxic condit...

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Main Authors:	Subang, Maria C., Fatah, Rewas, Bright, Carly, Blanco, Patricia, Berenstein, Mariana, Wu, Ying, Podhajcer, Osvaldo L., Winyard, Paul G., Chernajovsky, Yuti, Gould, David
Format:	Online
Language:	English
Published:	Springer-Verlag 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308011/

id	pubmed-3308011
recordtype	oai_dc
spelling	pubmed-33080112012-03-22 A novel hybrid promoter responsive to pathophysiological and pharmacological regulation Subang, Maria C. Fatah, Rewas Bright, Carly Blanco, Patricia Berenstein, Mariana Wu, Ying Podhajcer, Osvaldo L. Winyard, Paul G. Chernajovsky, Yuti Gould, David Original Article The aim of this study was to construct a promoter containing DNA motifs for an endogenous transcription factor associated with inflammation along with motifs for pharmacological regulation factors. We demonstrate in transfected cells that expression of a gene of interest is induced by hypoxic conditions or through pharmacological induction, and also show pharmacological repression. In vivo studies utilised electroporation of plasmid to mouse paws, a delivery method shown to be effective by bioluminescence imaging. For gene therapy, the promoter was used to drive expression of IL-1Ra in a paw inflammation model with therapeutic effect observed which was further enhanced when the promoter was additionally induced with a pharmacological activator. One of the most important observations from this study was that promoter induction by hypoxia or inflammation could be prevented by the pharmacological repressor in the absence of doxycycline. These studies demonstrate that hybrid promoters enable pharmacological adjustment to the pathophysiological level of gene expression and, importantly, that they allow termination of gene expression even in the presence of pathophysiological stimuli. Springer-Verlag 2011-10-30 2012-04 /pmc/articles/PMC3308011/ /pubmed/22038171 http://dx.doi.org/10.1007/s00109-011-0826-3 Text en © The Author(s) 2011
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Subang, Maria C. Fatah, Rewas Bright, Carly Blanco, Patricia Berenstein, Mariana Wu, Ying Podhajcer, Osvaldo L. Winyard, Paul G. Chernajovsky, Yuti Gould, David
spellingShingle	Subang, Maria C. Fatah, Rewas Bright, Carly Blanco, Patricia Berenstein, Mariana Wu, Ying Podhajcer, Osvaldo L. Winyard, Paul G. Chernajovsky, Yuti Gould, David A novel hybrid promoter responsive to pathophysiological and pharmacological regulation
author_facet	Subang, Maria C. Fatah, Rewas Bright, Carly Blanco, Patricia Berenstein, Mariana Wu, Ying Podhajcer, Osvaldo L. Winyard, Paul G. Chernajovsky, Yuti Gould, David
author_sort	Subang, Maria C.
title	A novel hybrid promoter responsive to pathophysiological and pharmacological regulation
title_short	A novel hybrid promoter responsive to pathophysiological and pharmacological regulation
title_full	A novel hybrid promoter responsive to pathophysiological and pharmacological regulation
title_fullStr	A novel hybrid promoter responsive to pathophysiological and pharmacological regulation
title_full_unstemmed	A novel hybrid promoter responsive to pathophysiological and pharmacological regulation
title_sort	novel hybrid promoter responsive to pathophysiological and pharmacological regulation
description	The aim of this study was to construct a promoter containing DNA motifs for an endogenous transcription factor associated with inflammation along with motifs for pharmacological regulation factors. We demonstrate in transfected cells that expression of a gene of interest is induced by hypoxic conditions or through pharmacological induction, and also show pharmacological repression. In vivo studies utilised electroporation of plasmid to mouse paws, a delivery method shown to be effective by bioluminescence imaging. For gene therapy, the promoter was used to drive expression of IL-1Ra in a paw inflammation model with therapeutic effect observed which was further enhanced when the promoter was additionally induced with a pharmacological activator. One of the most important observations from this study was that promoter induction by hypoxia or inflammation could be prevented by the pharmacological repressor in the absence of doxycycline. These studies demonstrate that hybrid promoters enable pharmacological adjustment to the pathophysiological level of gene expression and, importantly, that they allow termination of gene expression even in the presence of pathophysiological stimuli.
publisher	Springer-Verlag
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308011/
_version_	1611515487291703296

A novel hybrid promoter responsive to pathophysiological and pharmacological regulation

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