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Article: Hepatocyte nuclear factor 1 binding element within the promoter of microsomal triglyceride transfer protein (MTTP) gene is crucial for MTTP basal expression and insulin responsiveness

TitleHepatocyte nuclear factor 1 binding element within the promoter of microsomal triglyceride transfer protein (MTTP) gene is crucial for MTTP basal expression and insulin responsiveness
Authors
Issue Date2008
PublisherSociety for Endocrinology. The Journal's web site is located at http://jme.endocrinology-journals.org/
Citation
Journal of Molecular Endocrinology, 2008, v. 41 n. 4, p. 229-238 How to Cite?
AbstractInsulin inhibits the transcription of the microsomal triglyceride transfer protein (MTTP), which plays a pivotal role in lipoprotein assembly and secretion. Here, we provide evidence that a hepatocyte nuclear factor 1 binding element (HNF1 A element) within the MTTP promoter serves as a novel negative insulin-responsive element. Deletion/ mutation mapping of the MTTP gene promoter identified a modified HNF1A element that is crucial to the negative insulin effect. Chimeric promoter containing this HNF1A element and minimal TEAD1 promoter also responded negatively toward insulin treatment. Gel shift assay demonstrated that HNF1A but not HNF1 B binds to this element. Enforced expression of HNF1A was sufficient to reconstitute the negative insulin responsiveness of MTTP promoter in TM4SF1 myocytes that are HNF1A negative. Furthermore, replacing this element with consensus HNF1A element preserved the negative insulin response, suggesting that negative insulin responsiveness is a generic characteristic of HNF1A element. Given that many genes implicated in diabetes contain HNF1A element, the potential regulation of these genes by insulin via HNF1A element may provide important clues for the manifestation and treatment of diabetic metabolic syndromes. © 2008 Society for Endocrinology.
Persistent Identifierhttp://hdl.handle.net/10722/148589
ISSN
2015 Impact Factor: 2.947
2015 SCImago Journal Rankings: 1.674
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Special Administrative Region, ChinaHKU7642/05M
Li Ka Shing Institute of Health Sciences
Shanghai Metropolitan Fund for Research and Development04JC14096
Foundation Of Guangzhou Science and Technology Bureau2005Z1-E0131
Funding Information:

This work was supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (HKU7642/05M to M C L), and in part by Li Ka Shing Institute of Health Sciences (to H F K), Shanghai Metropolitan Fund for Research and Development (04JC14096), and Foundation Of Guangzhou Science and Technology Bureau (2005Z1-E0131).

References

 

DC FieldValueLanguage
dc.contributor.authorAu, WSen_HK
dc.contributor.authorLu, Len_HK
dc.contributor.authorYeung, CMen_HK
dc.contributor.authorLiu, CCen_HK
dc.contributor.authorWong, OGWen_HK
dc.contributor.authorLai, Len_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLin, MCen_HK
dc.date.accessioned2012-05-29T06:13:56Z-
dc.date.available2012-05-29T06:13:56Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal of Molecular Endocrinology, 2008, v. 41 n. 4, p. 229-238en_HK
dc.identifier.issn0952-5041en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148589-
dc.description.abstractInsulin inhibits the transcription of the microsomal triglyceride transfer protein (MTTP), which plays a pivotal role in lipoprotein assembly and secretion. Here, we provide evidence that a hepatocyte nuclear factor 1 binding element (HNF1 A element) within the MTTP promoter serves as a novel negative insulin-responsive element. Deletion/ mutation mapping of the MTTP gene promoter identified a modified HNF1A element that is crucial to the negative insulin effect. Chimeric promoter containing this HNF1A element and minimal TEAD1 promoter also responded negatively toward insulin treatment. Gel shift assay demonstrated that HNF1A but not HNF1 B binds to this element. Enforced expression of HNF1A was sufficient to reconstitute the negative insulin responsiveness of MTTP promoter in TM4SF1 myocytes that are HNF1A negative. Furthermore, replacing this element with consensus HNF1A element preserved the negative insulin response, suggesting that negative insulin responsiveness is a generic characteristic of HNF1A element. Given that many genes implicated in diabetes contain HNF1A element, the potential regulation of these genes by insulin via HNF1A element may provide important clues for the manifestation and treatment of diabetic metabolic syndromes. © 2008 Society for Endocrinology.en_HK
dc.languageengen_US
dc.publisherSociety for Endocrinology. The Journal's web site is located at http://jme.endocrinology-journals.org/en_HK
dc.relation.ispartofJournal of Molecular Endocrinologyen_HK
dc.rightsJournal of Molecular Endocrinology. Copyright © Society for Endocrinology.-
dc.subject.meshBinding Sites - Geneticsen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCarrier Proteins - Genetics - Metabolismen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshElectrophoretic Mobility Shift Assayen_US
dc.subject.meshGene Expression - Drug Effectsen_US
dc.subject.meshHepatocyte Nuclear Factor 1 - Genetics - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoprecipitationen_US
dc.subject.meshInsulin - Pharmacologyen_US
dc.subject.meshMutationen_US
dc.subject.meshPromoter Regions, Genetic - Geneticsen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshResponse Elements - Geneticsen_US
dc.titleHepatocyte nuclear factor 1 binding element within the promoter of microsomal triglyceride transfer protein (MTTP) gene is crucial for MTTP basal expression and insulin responsivenessen_HK
dc.typeArticleen_HK
dc.identifier.emailLu, L: liweilu@hkucc.hku.hken_HK
dc.identifier.emailWong, OGW: wonggw@hkucc.hku.hken_HK
dc.identifier.emailLin, MC: mcllin@hkucc.hku.hk-
dc.identifier.authorityLu, L=rp00477en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1677/JME-08-0080en_HK
dc.identifier.pmid18697801-
dc.identifier.scopuseid_2-s2.0-55749104018en_HK
dc.identifier.hkuros148604-
dc.identifier.hkuros176936-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-55749104018&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume41en_HK
dc.identifier.issue3-4en_HK
dc.identifier.spage229en_HK
dc.identifier.epage238en_HK
dc.identifier.isiWOS:000260172800012-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridAu, WS=7202383097en_HK
dc.identifier.scopusauthoridLu, L=7403963552en_HK
dc.identifier.scopusauthoridYeung, CM=7201354151en_HK
dc.identifier.scopusauthoridLiu, CC=23492742300en_HK
dc.identifier.scopusauthoridWong, OG=7004813981en_HK
dc.identifier.scopusauthoridLai, L=12445800200en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.customcontrol.immutablesml 130620-

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