2016
Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny
Giebel N, Shadley J, McCarver D, Dorko K, Gramignoli R, Strom S, Yan K, Simpson P, Hines R. Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny. Drug Metabolism And Disposition 2016, 44: 1027-1037. PMID: 26921389, PMCID: PMC4931893, DOI: 10.1124/dmd.116.069344.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overBinding SitesChildChild, PreschoolChromatinChromatin Assembly and DisassemblyCytochrome P-450 CYP3AGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicGestational AgeHepatocytesHistonesHumansInfantLiverMiddle AgedNucleic Acid ConformationPromoter Regions, GeneticProtein ConformationStructure-Activity RelationshipTranscription, Genetic
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 hypermethylationNovel CYP2C9 Promoter Variants and Assessment of Their Impact on Gene Expression
Kramer M, Rettie A, Rieder M, Cabacungan E, Hines R. Novel CYP2C9 Promoter Variants and Assessment of Their Impact on Gene Expression. Molecular Pharmacology 2008, 73: 1751-1760. PMID: 18310303, PMCID: PMC2413059, DOI: 10.1124/mol.107.044149.Peer-Reviewed Original Research
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
2006
Identification and Functional Analysis of Common Human Flavin-Containing Monooxygenase 3 Genetic Variants
Koukouritaki S, Poch M, Henderson M, Siddens L, Krueger S, VanDyke J, Williams D, Pajewski N, Wang T, Hines R. Identification and Functional Analysis of Common Human Flavin-Containing Monooxygenase 3 Genetic Variants. Journal Of Pharmacology And Experimental Therapeutics 2006, 320: 266-273. PMID: 17050781, DOI: 10.1124/jpet.106.112268.Peer-Reviewed Original Research
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 elements
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 polymorphisms
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
1998
A Genetic Polymorphism in the Regulatory Sequences of HumanCYP2E1:Association with Increased Chlorzoxazone Hydroxylation in the Presence of Obesity and Ethanol Intake
McCarver D, Byun R, Hines R, Hichme M, Wegenek W. A Genetic Polymorphism in the Regulatory Sequences of HumanCYP2E1:Association with Increased Chlorzoxazone Hydroxylation in the Presence of Obesity and Ethanol Intake. Toxicology And Applied Pharmacology 1998, 152: 276-281. PMID: 9772223, DOI: 10.1006/taap.1998.8532.Peer-Reviewed Original ResearchConceptsMetabolic abilitiesDNA samplesHuman DNA samplesDNA insertionRegulatory sequencesRegulatory regionsXbaI fragmentGenomic probesRegulatory polymorphismsRestriction enzyme XbaIRestriction enzyme digestionSame DNA samplesInsertion mutationsUpstream regionRestriction enzymesSouthern blotFunctional significanceSouthern blottingMutationsEnzyme XbaIEnzyme digestionGenetic polymorphismsVivo CYP2E1 activityFunctional characterization of the human CYP1A1 negative regulatory element: modulation of Ah receptor mediated transcriptional activity.
Piechocki M, Hines R. Functional characterization of the human CYP1A1 negative regulatory element: modulation of Ah receptor mediated transcriptional activity. Carcinogenesis 1998, 19: 771-780. PMID: 9635862, DOI: 10.1093/carcin/19.5.771.Peer-Reviewed Original Research
1997
Further Characterization of the Major and Minor RabbitFMO1Promoters and Identification of both Positive and Negative Distal Regulatory Elements
Luo Z, Hines R. Further Characterization of the Major and Minor RabbitFMO1Promoters and Identification of both Positive and Negative Distal Regulatory Elements. Archives Of Biochemistry And Biophysics 1997, 346: 96-104. PMID: 9328289, DOI: 10.1006/abbi.1997.0287.Peer-Reviewed Original ResearchConceptsRegulatory domainRegulatory sequencesRegulatory regionsSpecific DNA/protein complexesDNA/protein complexesUpstream regulatory domainsDistal regulatory elementsNegative regulatory sequencesPositive regulatory domainUpstream regulatory sequencesNegative regulatory regionPositive regulatory regionBasal transcriptional activityProtein complexesTranscription initiationHepG2 nuclear extractsDeletion mutantsMature transcriptsDeletion analysisRegulatory elementsLeader sequenceMinor promoterTransient expressionUpstream promoterTranscriptional activity
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