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Article: Identification of a negative response element in the human inducible nitric oxide synthase (hiNOS) promoter: the role of NF-κB-repressing factor (NRF) in basal repression of the hiNOS gene

TitleIdentification of a negative response element in the human inducible nitric oxide synthase (hiNOS) promoter: the role of NF-κB-repressing factor (NRF) in basal repression of the hiNOS gene
Authors
Issue Date2002
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
National Academy of Sciences Proceedings, 2002, v. 99 n. 22, p. 14212-14217 How to Cite?
AbstractAlthough nuclear factor (NF)-κB plays a central role in mediating cytokine-stimulated human inducible nitric-oxide synthase (hiNOS) gene transcription, very little is known about the factors involved in silencing of the hiNOS promoter. NF-κB-repressing factor (NRF) interacts with a specific negative regulatory element (NRE) to mediate transcriptional repression of certain NF-κB responsive genes. By sequence comparison with the IFN-β and IL-8 promoters, we identified an NRE in the hiNOS promoter located at −6.7 kb upstream. In A549 and HeLa human cells, constitutive NRF mRNA expression is detected by RT-PCR. Gel shift assay showed constitutive NRF binding to the hiNOS NRE. Mutation of the −6.7-kb NRE site in the hiNOS promoter resulted in loss of NRF binding and increased basal but not cytokine-stimulated hiNOS transcription in promoter transfection experiments. Interestingly, overexpression of NRF suppressed both basal and cytokine-induced hiNOS promoter activity that depended on an intact cis-acting NRE motif. By using stably transformed HeLa cells with the tetracycline on/off expression system, reduction of cellular NRF by expressing antisense NRF increased basal iNOS promoter activity and resulted in constitutive iNOS mRNA expression. These data demonstrate that the transacting NRF protein is involved in constitutive silencing of the hiNOS gene by binding to a cis-acting NRE upstream in the hiNOS promoter.
Persistent Identifierhttp://hdl.handle.net/10722/49338
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFeng, Xen_HK
dc.contributor.authorGuo, Zen_HK
dc.contributor.authorNourbakhsh, Men_HK
dc.contributor.authorHauser, Hen_HK
dc.contributor.authorGanster, Ren_HK
dc.contributor.authorShao, Len_HK
dc.contributor.authorGeller, DAen_HK
dc.date.accessioned2008-06-12T06:39:49Z-
dc.date.available2008-06-12T06:39:49Z-
dc.date.issued2002en_HK
dc.identifier.citationNational Academy of Sciences Proceedings, 2002, v. 99 n. 22, p. 14212-14217en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49338-
dc.description.abstractAlthough nuclear factor (NF)-κB plays a central role in mediating cytokine-stimulated human inducible nitric-oxide synthase (hiNOS) gene transcription, very little is known about the factors involved in silencing of the hiNOS promoter. NF-κB-repressing factor (NRF) interacts with a specific negative regulatory element (NRE) to mediate transcriptional repression of certain NF-κB responsive genes. By sequence comparison with the IFN-β and IL-8 promoters, we identified an NRE in the hiNOS promoter located at −6.7 kb upstream. In A549 and HeLa human cells, constitutive NRF mRNA expression is detected by RT-PCR. Gel shift assay showed constitutive NRF binding to the hiNOS NRE. Mutation of the −6.7-kb NRE site in the hiNOS promoter resulted in loss of NRF binding and increased basal but not cytokine-stimulated hiNOS transcription in promoter transfection experiments. Interestingly, overexpression of NRF suppressed both basal and cytokine-induced hiNOS promoter activity that depended on an intact cis-acting NRE motif. By using stably transformed HeLa cells with the tetracycline on/off expression system, reduction of cellular NRF by expressing antisense NRF increased basal iNOS promoter activity and resulted in constitutive iNOS mRNA expression. These data demonstrate that the transacting NRF protein is involved in constitutive silencing of the hiNOS gene by binding to a cis-acting NRE upstream in the hiNOS promoter.en_HK
dc.format.extent386 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.rightsNational Academy of Sciences Proceedings. Copyright © National Academy of Sciences.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshDNA-Binding Proteinsen_HK
dc.subject.meshNF-κB - metabolismen_HK
dc.subject.meshNitric Oxide Synthase - geneticsen_HK
dc.subject.meshRepressor Proteins - genetics - metabolismen_HK
dc.subject.meshResponse Elementsen_HK
dc.titleIdentification of a negative response element in the human inducible nitric oxide synthase (hiNOS) promoter: the role of NF-κB-repressing factor (NRF) in basal repression of the hiNOS geneen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=99&issue=22&spage=14212&epage=14217&date=2002&atitle=Identification+of+a+negative+response+element+in+the+human+inducible+nitric+oxide+synthase+(hiNOS)+promoter:+the+role+of+NF-κB-repressing+factor+(NRF)+in+basal+repression+of+the+hiNOS+geneen_HK
dc.identifier.emailGanster, R: ganster@hkucc.hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1073/pnas.212306199en_HK
dc.identifier.pmid12381793-
dc.identifier.pmcidPMC137863en_HK
dc.identifier.scopuseid_2-s2.0-0037195139-
dc.identifier.isiWOS:000178967400046-

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