2008
Differential regulation of human hepatic flavin containing monooxygenase 3 (FMO3) by CCAAT/enhancer-binding protein β (C/EBPβ) liver inhibitory and liver activating proteins
Klick D, Shadley J, Hines R. Differential regulation of human hepatic flavin containing monooxygenase 3 (FMO3) by CCAAT/enhancer-binding protein β (C/EBPβ) liver inhibitory and liver activating proteins. Biochemical Pharmacology 2008, 76: 268-278. PMID: 18555208, DOI: 10.1016/j.bcp.2008.05.002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBase SequenceCCAAT-Enhancer-Binding Protein-betaCell Line, TumorCells, CulturedDNAEmbryo, MammalianFemaleHepatocyte Nuclear Factor 3-betaHepatocytesHumansInfantLiverMaleMiddle AgedMolecular Sequence DataMutagenesis, Site-DirectedOxygenasesPromoter Regions, GeneticProtein Structure, TertiarySequence AlignmentSequence Analysis, DNAConceptsNuclear proteinsLiver nuclear proteinsSpecific DNA/protein interactionsPromoter activityDNA-protein binding studiesDNA/protein interactionsDNA-protein interactionsTransient expression experimentsCell nuclear proteinsDNA methylase inhibitorCCAAT enhancer-binding proteinGene regulation studiesEnhancer-binding proteinNuclear protein extractsOxidative xenobiotic metabolismHepG2 cellsFMO3 expressionTranscriptional machineryChromatin immunoprecipitationProtein interactionsPromoter functionExpression experimentsMethylase inhibitorTransient expressionDNA hypermethylation
2007
Identification and Functional Analysis of a Novel Human CYP2E1 Far Upstream Enhancer
Shadley J, Divakaran K, Munson K, Hines R, Douglas K, McCarver D. Identification and Functional Analysis of a Novel Human CYP2E1 Far Upstream Enhancer. Molecular Pharmacology 2007, 71: 1630-1639. PMID: 17353354, DOI: 10.1124/mol.106.031302.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesCells, CulturedCytochrome P-450 CYP2E1Enhancer Elements, GeneticGATA4 Transcription FactorGene Expression Regulation, EnzymologicGenetic VariationHepatocytesHumansMolecular Sequence DataPromoter Regions, GeneticRepetitive Sequences, Nucleic AcidSteroidogenic Factor 1Trans-ActivatorsTranscriptional ActivationConceptsElectrophoretic mobility shift assaysEnhancer sequencesCompetitive electrophoretic mobility shift assaysSupershift electrophoretic mobility shift assaysFunctional regulatory elementsGATA family membersMobility shift assaysGreater luciferase activityOrphan nuclear receptorSteroidogenic factor 1Luciferase reporter activityGATA sequencesFetoprotein transcription factorGATA familyChromatin immunoprecipitationTranscription factorsNuclear proteinsRegulatory elementsShift assaysRegulatory mechanismsFunctional analysisPromoter constructsDirect repeatsReporter activityUpstream region
2005
MOLECULAR MECHANISMS REGULATING HUMAN CYP4B1 LUNG-SELECTIVE EXPRESSION
Poch M, Cutler N, Yost G, Hines R. MOLECULAR MECHANISMS REGULATING HUMAN CYP4B1 LUNG-SELECTIVE EXPRESSION. Drug Metabolism And Disposition 2005, 33: 1174-1184. PMID: 15900016, DOI: 10.1124/dmd.105.004523.Peer-Reviewed Original ResearchConceptsDistal regulatory elementsRegulatory elementsTransient expressionCompetitive electrophoretic mobility shift assaysDNA/protein binding assaysKrüppel-like factor (KLF) familyElectrophoretic mobility shift assaysTranscription factor recognition sequenceChromatin immunoprecipitation assaysTranscription factor sitesProximal elementMobility shift assaysHepG2 hepatoblastoma cellsProtein binding assaysSp1 bindingSp1 elementImmunoprecipitation assaysNuclear proteinsKidney-derived cellsFactor familyShift assaysFactor sitesMutagenesis studiesRegulatory mechanismsMolecular mechanismsSP1 AND SP3 REGULATE BASAL TRANSCRIPTION OF THE HUMAN CYP2F1 GENE
Wan J, Carr B, Cutler N, Lanza D, Hines R, Yost G. SP1 AND SP3 REGULATE BASAL TRANSCRIPTION OF THE HUMAN CYP2F1 GENE. Drug Metabolism And Disposition 2005, 33: 1244-1253. PMID: 15860659, DOI: 10.1124/dmd.105.004069.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesCell Line, TumorCytochrome P-450 Enzyme SystemCytochrome P450 Family 2DNAGene Expression RegulationGenes, ReporterHumansLuciferasesLungMolecular Sequence DataPromoter Regions, GeneticRepressor ProteinsSp1 Transcription FactorSp3 Transcription FactorTranscription, GeneticTranscriptional ActivationTransfectionConceptsSp3 expression vectorsExpression vectorCYP2F1 geneDrosophila Schneider line 2 cellsSchneider line 2 cellsSpecific protein-DNA complexesSp1 expression vectorSL-2 cellsProtein-DNA complexesProtein-DNA bindingTATA-less promoter regionA549 cellsCell nuclear extractsCompetitive electrophoretic mobilityBasal transcription elementProximal promoter elementsLuciferase reporter constructsSp1-like sitesSp3 factorsSp3 proteinsSelective transcriptionSupershift studiesGene transcriptionPromoter elementsTranscription elementsDiscovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants
Koukouritaki S, Poch M, Cabacungan E, McCarver D, Hines R. Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants. Molecular Pharmacology 2005, 68: 383-392. PMID: 15858076, DOI: 10.1124/mol.105.012062.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell Line, TumorGenetic VariationHaplotypesHumansMolecular Sequence DataOxygenasesPenaeidaePolymorphism, Single NucleotideConceptsFlavin-containing monooxygenasesFunctional analysisSingle nucleotide polymorphism (SNP) discoveryMembrane interaction domainHaplotype variantsSite-directed mutagenesisConsensus splice sitesFMO3 expressionUpstream SNPsGene functionPolymorphism discoveryNear complete lossRossmann foldFAD bindingInteraction domainSingle nucleotide polymorphismsRegion haplotypesHaplotype 8Exon SNPsFMO enzymesPromoter activityIntron SNPSequence analysisSNP frequenciesLuciferase construct
2003
Genetic Variability at the Human FMO1 Locus: Significance of a Basal Promoter Yin Yang 1 Element Polymorphism (FMO1*6)
Hines R, Luo Z, Hopp K, Cabacungan E, Koukouritaki S, McCarver D. Genetic Variability at the Human FMO1 Locus: Significance of a Basal Promoter Yin Yang 1 Element Polymorphism (FMO1*6). Journal Of Pharmacology And Experimental Therapeutics 2003, 306: 1210-1218. PMID: 12829732, DOI: 10.1124/jpet.103.053686.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsFlavin-containing monooxygenasesGenetic variabilityIntron 1 splice donor siteElectrophoretic mobility shift assaysYin Yang 1 (YY1) transcription factorTransient expression assaysCore binding sequenceATG start codonMobility shift assaysSplice donor siteCommon single nucleotide polymorphismsYY1 bindingStructural geneTranscription factorsStart codonShift assaysExonic sequencesChromosome 1q23Binding sequenceExpression assaysPromoter activityVariety of toxicantsBase pairsNucleotide polymorphismsCharacterization of the Human Lung CYP2F1 Gene and Identification of a Novel Lung-specific Binding Motif*
Carr B, Wan J, Hines R, Yost G. Characterization of the Human Lung CYP2F1 Gene and Identification of a Novel Lung-specific Binding Motif*. Journal Of Biological Chemistry 2003, 278: 15473-15483. PMID: 12598524, DOI: 10.1074/jbc.m300319200.Peer-Reviewed Original ResearchConceptsCYP2F1 geneCompetitive electrophoretic mobility shift assaysBacterial artificial chromosome (BAC) clonesElectrophoretic mobility shift assaysDNA-protein complexesE-box motifArtificial chromosome clonesPrimer extension analysisTranscription start siteTissue-specific expressionDNA consensus siteMobility shift assaysTissue-specific regulationUntranslated exon 1Transient transfection studiesLuciferase reporter constructsBox motifChromosome clonesConsensus sitesE-boxNuclear proteinsStart siteExtension analysisCDNA endsUpstream sequencesGenotyping and site-directed mutagenesis of a cytochrome P450 meander Pro-X-Arg motif critical to CYP4B1 catalysis
Zheng Y, Henne K, Charmley P, Kim R, McCarver D, Cabacungan E, Hines R, Rettie A. Genotyping and site-directed mutagenesis of a cytochrome P450 meander Pro-X-Arg motif critical to CYP4B1 catalysis. Toxicology And Applied Pharmacology 2003, 186: 119-126. PMID: 12639503, DOI: 10.1016/s0041-008x(02)00028-5.Peer-Reviewed Original ResearchConceptsHeme bindingArg motifAmino acid sequence alignmentNonhuman primate speciesPrimate speciesRedox partner interactionsSite-directed mutagenesisCYP4B1 geneRestriction enzyme fragment length polymorphismArg triadFragment length polymorphismRabbit CYP4B1Sequence alignmentHuman allelesN-terminalCatalytic functionCommon laboratory animalsAmino acidsPro residuesLength polymorphismMeander regionHuman populationDistal ArgGenesGlu-Arg
2002
Alternative Processing of the Human FMO6 Gene Renders Transcripts Incapable of Encoding a Functional Flavin-Containing Monooxygenase
Hines R, Hopp K, Franco J, Saeian K, Begun F. Alternative Processing of the Human FMO6 Gene Renders Transcripts Incapable of Encoding a Functional Flavin-Containing Monooxygenase. Molecular Pharmacology 2002, 62: 320-325. PMID: 12130684, DOI: 10.1124/mol.62.2.320.Peer-Reviewed Original ResearchGENETIC POLYMORPHISMS OF FLAVIN-CONTAINING MONOOXYGENASE (FMO)
Krueger S, Williams D, Yueh M, Martin S, Hines R, Raucy J, Dolphin C, Shephard E, Phillips I. GENETIC POLYMORPHISMS OF FLAVIN-CONTAINING MONOOXYGENASE (FMO). Drug Metabolism Reviews 2002, 34: 523-532. PMID: 12214664, DOI: 10.1081/dmr-120005653.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceEthnicityGenotypeHumansIsoenzymesMethylaminesMolecular Sequence DataMultigene FamilyOxygenasesPolymorphism, GeneticXenobioticsConceptsFlavin-Containing MonooxygenaseAdult human liverPercent of individualsPlethora of drugsTrimethylamine N-oxygenationDrug metabolismHuman liverGenetic polymorphismsHispanic descentPremature stop codonPolymorphic expressionLungPreliminary evidenceFunctional FMO2African descentXenobiotic toxicityMammalian flavinN-oxygenationFMO2TrimethylaminuriaEthylene thioureaPolymorphismAllelesPatientsExpression
2001
Regulation of Flavin-Containing Monooxygenase 1 Expression by Ying Yang 1 and Hepatic Nuclear Factors 1 and 4
Luo Z, Hines R. Regulation of Flavin-Containing Monooxygenase 1 Expression by Ying Yang 1 and Hepatic Nuclear Factors 1 and 4. Molecular Pharmacology 2001, 60: 1421-1430. PMID: 11723251, DOI: 10.1124/mol.60.6.1421.Peer-Reviewed Original ResearchAnimalsBase SequenceDNA-Binding ProteinsEnhancer Elements, GeneticErythroid-Specific DNA-Binding FactorsGene Expression Regulation, EnzymologicHepatocyte Nuclear Factor 1Hepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaHumansMolecular Sequence DataNuclear ProteinsOxygenasesPromoter Regions, GeneticRabbitsSequence Homology, Nucleic AcidTranscription FactorsTransfectionTumor Cells, CulturedYY1 Transcription Factor
2000
Regulation of DHP receptor expression by elements in the 5′-flanking sequence
Liu L, Fan Q, El-Zaru M, Vanderpool K, Hines R, Marsh J. Regulation of DHP receptor expression by elements in the 5′-flanking sequence. AJP Heart And Circulatory Physiology 2000, 278: h1153-h1162. PMID: 10749709, DOI: 10.1152/ajpheart.2000.278.4.h1153.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated Regions8-Bromo Cyclic Adenosine MonophosphateAdrenergic alpha-AgonistsAdrenergic beta-AgonistsAnimalsBase SequenceCalcium Channels, L-TypeCells, CulturedElectrophoresisGene ExpressionGenes, ReporterGenetic Complementation TestGonadal Steroid HormonesIn Vitro TechniquesIsoproterenolLuciferasesMolecular Sequence DataMuscle Fibers, SkeletalMuscle, Smooth, VascularMyocardiumPhenylephrinePromoter Regions, GeneticRatsRNA, MessengerTestosteroneTranscription, GeneticTransfectionConceptsNeonatal rat cardiac ventricular myocytesVascular smooth muscle cellsRat cardiac ventricular myocytesSmooth muscle cellsCardiac ventricular myocytesCardiac-specific transcription factor Nkx2.5Receptor expressionResponse elementTranscription factor Nkx2.5Hormone responsivenessVentricular myocytesMuscle cellsSubunit gene promoterModulating activityHormone response elementsCAMP response elementPromoter-luciferase reporter gene constructsGene promoterTransient transfection experimentsRatsFusion geneSubunit geneAP-1 site
1996
Identification of Multiple Rabbit Flavin-Containing Monooxygenase Form 1 (FMO1) Gene Promoters and Observation of Tissue-Specific DNase I Hypersensitive Sites
Luo Z, Hines R. Identification of Multiple Rabbit Flavin-Containing Monooxygenase Form 1 (FMO1) Gene Promoters and Observation of Tissue-Specific DNase I Hypersensitive Sites. Archives Of Biochemistry And Biophysics 1996, 336: 251-260. PMID: 8954572, DOI: 10.1006/abbi.1996.0555.Peer-Reviewed Original ResearchIdentification of tissue-specific DNase I hypersensitive sites in the rabbit flavin-containing monooxygenase form 2 gene.
Shehin-Johnson S, Palmer K, Hines R. Identification of tissue-specific DNase I hypersensitive sites in the rabbit flavin-containing monooxygenase form 2 gene. Drug Metabolism And Disposition 1996, 24: 891-8. PMID: 8869825.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCloning, MolecularDeoxyribonuclease IDNADNA MethylationLungMolecular Sequence DataOxygenasesPromoter Regions, GeneticRabbitsConceptsDNase IHypersensitive sitesTissue-specific transcription factorsLambda EMBL3 genomic libraryPolyomavirus enhancer activator 3Base pairsTissue-specific DNase I hypersensitive siteDNase I hypersensitive sitesTissue-specific DNase IEMBL3 genomic libraryPrimer extension analysisTranscription start siteClassical TATA boxTissue-specific mannerHypersensitive domainGenomic clonesGenomic libraryMethylated regionsTranscription factorsCDNA sequenceKilobase pairsStart siteTATA boxExtension analysisType II cell populations
1995
Partial Characterization of the Human CYP1A1 Negatively Acting Transcription Factor and Mutational Analysis of Its Cognate DNA Recognition Sequence
Boucher P, Piechocki M, Hines R. Partial Characterization of the Human CYP1A1 Negatively Acting Transcription Factor and Mutational Analysis of Its Cognate DNA Recognition Sequence. Molecular And Cellular Biology 1995, 15: 5144-5151. PMID: 7651431, PMCID: PMC230761, DOI: 10.1128/mcb.15.9.5144.Peer-Reviewed Original ResearchBase SequenceBinding SitesBinding, CompetitiveCells, CulturedCytochrome P-450 Enzyme SystemDNA Mutational AnalysisGene Expression Regulation, EnzymologicHumansMolecular Sequence DataNuclear ProteinsOxygenasesProtein BindingRegulatory Sequences, Nucleic AcidSequence Homology, Nucleic AcidTranscription FactorsTissue-specific expression of flavin-containing monooxygenase (FMO) forms 1 and 2 in the rabbit.
Shehin-Johnson S, Williams D, Larsen-Su S, Stresser D, Hines R. Tissue-specific expression of flavin-containing monooxygenase (FMO) forms 1 and 2 in the rabbit. Journal Of Pharmacology And Experimental Therapeutics 1995, 272: 1293-9. PMID: 7891346.Peer-Reviewed Original ResearchIn vitro binding and functional studies comparing the human CYPIAI negative regulatory element with the orthologous sequences from rodent genes
Boucher P, Hines R. In vitro binding and functional studies comparing the human CYPIAI negative regulatory element with the orthologous sequences from rodent genes. Carcinogenesis 1995, 16: 383-392. PMID: 7859371, DOI: 10.1093/carcin/16.2.383.Peer-Reviewed Original ResearchConceptsNegative regulatory elementSpecific DNA-protein complexesDNA-protein complexesTransient expression assaysRegulatory elementsNuclear proteinsMouse fragmentsHeterologous promoterExpression assaysCell linesElectrophoretic mobility shift assaysMouse nuclear proteinMouse CYP1A1 geneSouthwestern blot analysisMobility shift assaysCYP1A1 geneNegative regulatory activitySimilar protection patternMouse hepatoma cell lineRodent cell linesCytosine-rich sequencesCytosine-rich regionsHuman CYP1A1 geneOrthologous sequencesRodent genes
1994
Restoration of aryl hydrocarbon (Ah) responsiveness in MDA-MB-231 human breast cancer cells by transient expression of the estrogen receptor
Thomsen J, Wang X, Hines R, Safe S. Restoration of aryl hydrocarbon (Ah) responsiveness in MDA-MB-231 human breast cancer cells by transient expression of the estrogen receptor. Carcinogenesis 1994, 15: 933-937. PMID: 8200098, DOI: 10.1093/carcin/15.5.933.Peer-Reviewed Original ResearchConceptsMDA-MB-231 cellsHuman breast cancer cellsMDA-MB-231 human breast cancer cellsAh-responsivenessBreast cancer cellsNM TCDDHuman estrogen receptor expression plasmidAryl hydrocarbon responsivenessCancer cellsReceptor expression plasmidAryl hydrocarbon receptorProgesterone receptorEstrogen receptorResponsive plasmidCYP1A1 gene expressionHydrocarbon receptorReceptorsCell linesCYP1A1 geneCAT activityExpression of nuclearParallel studyHuman CYP1A1 geneCellsExpression plasmid
1993
Expression of human cytochrome P450 1A1 in DNA repair deficient and proficient human fibroblasts stably transformed with an inducible expression vector
States J, Quan T, Hines R, Novak R, Runge-Morris M. Expression of human cytochrome P450 1A1 in DNA repair deficient and proficient human fibroblasts stably transformed with an inducible expression vector. Carcinogenesis 1993, 14: 1643-1649. PMID: 8353849, DOI: 10.1093/carcin/14.8.1643.Peer-Reviewed Original ResearchMeSH Keywords7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideAnimalsBase SequenceBenzo(a)pyreneBenzoflavonesBiotransformationCadmiumCadmium CompoundsChimeraCytochrome P-450 Enzyme SystemDNA RepairEnzyme InductionFibroblastsGene Expression Regulation, EnzymologicGenetic VectorsHumansIsoenzymesMiceMolecular Sequence DataPlasmidsRNA, MessengerSulfatesTransfectionTransformation, GeneticXeroderma PigmentosumConceptsCytochrome P450 1A1P450 1A1Inducible CYP1A1Inducible mouse metallothionein-I promoterLow dosesHuman skin fibroblastsProficient cellsPotent mutagenic agentCYP1A1 expressionCYP1A1 activityHuman cytochrome P450 1A1DNA repairCYP1A1Mouse metallothionein-I promoterCytotoxic effectsMetallothionein-I promoterSkin fibroblastsDifferential cytotoxicityDNA repair-proficient cellsToxic effectsMore cytotoxicCytochrome P450Normal cellsRepairHuman CYP1A1Specific nuclear protein binding to a negative regulatory element on the human CYP1A1 gene
Boucher P, Ruch R, Hines R. Specific nuclear protein binding to a negative regulatory element on the human CYP1A1 gene. Journal Of Biological Chemistry 1993, 268: 17384-17391. PMID: 8349622, DOI: 10.1016/s0021-9258(19)85346-2.Peer-Reviewed Original ResearchConceptsNegative regulatory activityNuclear proteinsElectrophoretic mobility shift assaysCellular trans-acting factorsTrans-acting factorsRegulatory activityStrand-specific mannerCo-transfection studiesMethylation interference experimentsMobility shift assaysNegative regulatory elementSpecific nuclear proteinCytosine-rich sequencesHuman CYP1A1 genePromoter/enhancerRegulatory elementsShift assaysTransient expressionReporter geneDNase IChimeric plasmidsCYP1A1 promoterImportant sequencesCYP1A1 genePalindromes