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Article: Involvement of NF-κB subunit p65 and retinoic acid receptors, RARα and RXRα, in transcriptional regulation of the human GnRH II gene

TitleInvolvement of NF-κB subunit p65 and retinoic acid receptors, RARα and RXRα, in transcriptional regulation of the human GnRH II gene
Authors
KeywordsGonadotropin-releasing hormone II
NF-κB subunit p65
Retinoic acid receptors
Silencer
Transcriptional regulation
Issue Date2007
PublisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.febsjournal.org/
Citation
FEBS Journal, 2007, v. 274 n. 11, p. 2695-2706 How to Cite?
AbstractGonadotropin-releasing hormone (GnRH) I and II are hypothalamic decapeptides with pivotal roles in the development of reproductive competence and regulation of reproductive events. In this study, transcriptional regulation of the human GnRH II gene was investigated. By scanning mutation analysis coupled with transient promoter assays, the motif at -641/-636 (CATGCC, designated GII-Sil) was identified as a repressor element. Mutation of this motif led to full restoration of promoter activity in TE671 medulloblastoma and JEG-3 placenta choriocarcinoma cells. Supershift and chromatin immunoprecipitation assays showed in vitro and in vivo binding of NF-κB subunit p65 and the retinoic acid receptors, RARα and RXRα, to the promoter sequences. Over-expression of these protein factors indicated that p65 is a potent repressor, and the RARα/RXRα heterodimer is involved in the differential regulation of the GnRH II gene in neuronal and placental cells. This was confirmed by quantitative real-time PCR. Treatment of cells with the RARα/RXRα ligands, all-trans retinoic acid and 9-cis-retinoic acid, reduced and increased GnRH II gene expression in TE671 and JEG-3 cells, respectively. Taken together, these data demonstrate the differential roles of NF-κB p65 and RARα/RXRα, interacting with the same sequence in the promoter of the human GnRH II gene to influence gene expression in a cell-specific manner. © 2007 The Authors.
Persistent Identifierhttp://hdl.handle.net/10722/91433
ISSN
2015 Impact Factor: 4.237
2015 SCImago Journal Rankings: 2.141
ISI Accession Number ID
References
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DC FieldValueLanguage
dc.contributor.authorHoo, RLCen_HK
dc.contributor.authorChan, KYYen_HK
dc.contributor.authorLeung, FKYen_HK
dc.contributor.authorLee, LTOen_HK
dc.contributor.authorLeung, PCKen_HK
dc.contributor.authorChow, BKCen_HK
dc.date.accessioned2010-09-17T10:19:19Z-
dc.date.available2010-09-17T10:19:19Z-
dc.date.issued2007en_HK
dc.identifier.citationFEBS Journal, 2007, v. 274 n. 11, p. 2695-2706en_HK
dc.identifier.issn1742-464Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/91433-
dc.description.abstractGonadotropin-releasing hormone (GnRH) I and II are hypothalamic decapeptides with pivotal roles in the development of reproductive competence and regulation of reproductive events. In this study, transcriptional regulation of the human GnRH II gene was investigated. By scanning mutation analysis coupled with transient promoter assays, the motif at -641/-636 (CATGCC, designated GII-Sil) was identified as a repressor element. Mutation of this motif led to full restoration of promoter activity in TE671 medulloblastoma and JEG-3 placenta choriocarcinoma cells. Supershift and chromatin immunoprecipitation assays showed in vitro and in vivo binding of NF-κB subunit p65 and the retinoic acid receptors, RARα and RXRα, to the promoter sequences. Over-expression of these protein factors indicated that p65 is a potent repressor, and the RARα/RXRα heterodimer is involved in the differential regulation of the GnRH II gene in neuronal and placental cells. This was confirmed by quantitative real-time PCR. Treatment of cells with the RARα/RXRα ligands, all-trans retinoic acid and 9-cis-retinoic acid, reduced and increased GnRH II gene expression in TE671 and JEG-3 cells, respectively. Taken together, these data demonstrate the differential roles of NF-κB p65 and RARα/RXRα, interacting with the same sequence in the promoter of the human GnRH II gene to influence gene expression in a cell-specific manner. © 2007 The Authors.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.febsjournal.org/en_HK
dc.relation.ispartofFEBS Journalen_HK
dc.rightsThe FEBS Journal. Copyright © Blackwell Publishing Ltd.-
dc.subjectGonadotropin-releasing hormone IIen_HK
dc.subjectNF-κB subunit p65en_HK
dc.subjectRetinoic acid receptorsen_HK
dc.subjectSilenceren_HK
dc.subjectTranscriptional regulationen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshDimerizationen_HK
dc.subject.meshDown-Regulationen_HK
dc.subject.meshElectrophoretic Mobility Shift Assayen_HK
dc.subject.meshGene Expression Regulationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshPromoter Regions, Genetic - drug effectsen_HK
dc.subject.meshReceptors, LHRH - biosynthesis - geneticsen_HK
dc.subject.meshReceptors, Retinoic Acid - physiologyen_HK
dc.subject.meshRetinoid X Receptor alpha - physiologyen_HK
dc.subject.meshTranscription Factor RelA - physiologyen_HK
dc.subject.meshTretinoin - pharmacologyen_HK
dc.titleInvolvement of NF-κB subunit p65 and retinoic acid receptors, RARα and RXRα, in transcriptional regulation of the human GnRH II geneen_HK
dc.typeArticleen_HK
dc.identifier.emailHoo, RLC: rubyhoo@hkucc.hku.hken_HK
dc.identifier.emailLee, LTO: ltolee2@hkucc.hku.hken_HK
dc.identifier.emailChow, BKC: bkcc@hku.hken_HK
dc.identifier.authorityHoo, RLC=rp01334en_HK
dc.identifier.authorityLee, LTO=rp00727en_HK
dc.identifier.authorityChow, BKC=rp00681en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1742-4658.2007.05804.xen_HK
dc.identifier.pmid17451432en_HK
dc.identifier.scopuseid_2-s2.0-34249036100en_HK
dc.identifier.hkuros130573-
dc.identifier.hkuros129117-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34249036100&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume274en_HK
dc.identifier.issue11en_HK
dc.identifier.spage2695en_HK
dc.identifier.epage2706en_HK
dc.identifier.eissn1742-4658-
dc.identifier.isiWOS:000246681900002-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectA conditional knockout animal model for secretin-
dc.relation.projectSecretin: a putative neurosecretory hormone that regulates water homeostasis in the hypothalamus-pituitary-adrenal axis-
dc.identifier.scopusauthoridHoo, RLC=6602369766en_HK
dc.identifier.scopusauthoridChan, KYY=25225022200en_HK
dc.identifier.scopusauthoridLeung, FKY=16317013200en_HK
dc.identifier.scopusauthoridLee, LTO=8367269000en_HK
dc.identifier.scopusauthoridLeung, PCK=12782513900en_HK
dc.identifier.scopusauthoridChow, BKC=7102826193en_HK
dc.identifier.citeulike1332756-

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