2018
Pklr Intron Splicing-Associated Mutations and Alternate Diagnoses Are Common in Pyruvate Kinase Deficient Patients with Single or No Pklr Coding Mutations
Lezon-Geyda K, Rose M, McNaull M, Knoll C, Yaish H, Pastore Y, Fermi E, Glader B, Bianchi P, Grace R, Gallagher P. Pklr Intron Splicing-Associated Mutations and Alternate Diagnoses Are Common in Pyruvate Kinase Deficient Patients with Single or No Pklr Coding Mutations. Blood 2018, 132: 3607. DOI: 10.1182/blood-2018-99-117805.Peer-Reviewed Original ResearchWhole-genome sequencingPyruvate kinase-deficient patientsSplice siteDonor splice sitePyruvate kinasePK-deficient patientsGenome sequencingPKLR geneSequence analysisWhole-exome sequencingIntron mutationsDominant negative phenotypeExon 7Exon 10Detailed sequence analysisPyruvate kinase geneDisease-associated variantsRare genetic variantsNormal mRNA processingSplice acceptor siteRegion mutationsIntron retentionErythroid promoterGenome databasePremature chain termination
2010
Mutation of a barrier insulator in the human ankyrin-1 gene is associated with hereditary spherocytosis
Gallagher PG, Steiner LA, Liem RI, Owen AN, Cline AP, Seidel NE, Garrett LJ, Bodine DM. Mutation of a barrier insulator in the human ankyrin-1 gene is associated with hereditary spherocytosis. Journal Of Clinical Investigation 2010, 120: 4453-4465. PMID: 21099109, PMCID: PMC2993586, DOI: 10.1172/jci42240.Peer-Reviewed Original ResearchConceptsAnkyrin-1 geneBarrier insulatorsTransgenic miceUpstream regionErythroid promoterChromatin configurationGene promoterErythroid cellsHereditary spherocytosisPotential pathogenetic mechanismsHuman ankyrin-1 geneHuman erythroid cell lineBarrier-associated proteinsErythroid cell linesPathogenetic mechanismsCommon causeUniform expressionNucleotide substitutionsRegion upstreamPromoter actsHuman diseasesPromoterCell linesPrimary cellsGenes
2008
Insulator Elements in Erythrocyte Membrane Genes
Steiner L, Maksimova Y, Lin J, Owen A, Schulz V, Bodine D, Gallagher P. Insulator Elements in Erythrocyte Membrane Genes. Blood 2008, 112: 3584. DOI: 10.1182/blood.v112.11.3584.3584.Peer-Reviewed Original ResearchErythrocyte membrane protein genesPosition-effect variegationMembrane protein geneProtein geneChromatin domainsAnkyrin promoterDNA sequencesErythroid cellsInsulator elementsMapping protein-DNA interactionsHeterochromatin-mediated geneGenome-wide scaleGenomic DNA microarrayBinding of CTCFStage-specific transcriptsEnhancer-blocking functionProtein-DNA interactionsCopy number-dependent expressionTissue-specific expressionProtein gene expressionCTCF occupancyRepetitive DNAInsulator functionSeparate enhancersErythroid promoter
2005
GATA-1 and Oct-1 Are Required for Expression of the Human α-Hemoglobin-stabilizing Protein Gene*
Gallagher PG, Liem RI, Wong E, Weiss MJ, Bodine DM. GATA-1 and Oct-1 Are Required for Expression of the Human α-Hemoglobin-stabilizing Protein Gene*. Journal Of Biological Chemistry 2005, 280: 39016-39023. PMID: 16186125, DOI: 10.1074/jbc.m506062200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBinding SitesBlood ProteinsCell LineCloning, MolecularDNA, ComplementaryErythropoiesisGATA1 Transcription FactorGene ExpressionGlobinsHeLa CellsHumansMiceMice, TransgenicMolecular ChaperonesMolecular Sequence DataMutationOctamer Transcription Factor-1Promoter Regions, GeneticRecombinant ProteinsRNA, MessengerConceptsAlpha-hemoglobin-stabilizing proteinGATA-1AHSP promoterAHSP genePromoter/reporter plasmidsGel mobility shift assaysAHSP gene expressionChromatin immunoprecipitation assaysErythroid-specific expressionMobility shift assaysFurther genetic studiesHuman tissue culture cell linesErythroid proteinTissue culture cell linesErythroid promoterNonerythroid tissuesProtein geneImmunoprecipitation assaysRegulatory elementsShift assaysGene promoterReporter geneCandidate genesDNase IGene expressionA dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis
Gallagher PG, Nilson DG, Wong C, Weisbein JL, Garrett-Beal LJ, Eber SW, Bodine DM. A dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis. Human Molecular Genetics 2005, 14: 2501-2509. PMID: 16037067, DOI: 10.1093/hmg/ddi254.Peer-Reviewed Original ResearchMeSH KeywordsAnkyrinsBase CompositionDNA PrimersErythrocyte MembraneGene Expression RegulationGenes, ReporterHumansPeptide Chain Initiation, TranslationalPolymerase Chain ReactionPolymorphism, Single-Stranded ConformationalPromoter Regions, GeneticSequence DeletionSpherocytosis, HereditaryTATA BoxTranscription Factor TFIIDTranscription, GeneticConceptsTFIID complex formationTATA-binding proteinTranscription initiation siteGene expressionAnkyrin promoterCis elementsInitiation siteCore promoter DNAMultiple transcription initiation sitesPreinitiation complex formationStart site utilizationComplex formationSite utilizationAlters gene expressionTFIID complexFunctional Sp1Promoter DNATranscription initiationTypes of promotersErythroid promoterMammalian promotersGene transcriptionTG deletionMutant promotersReporter gene
2004
Sequences Downstream of the Erythroid Promoter Are Required for High Level Expression of the Human α-Spectrin Gene*
Wong EY, Lin J, Forget BG, Bodine DM, Gallagher PG. Sequences Downstream of the Erythroid Promoter Are Required for High Level Expression of the Human α-Spectrin Gene*. Journal Of Biological Chemistry 2004, 279: 55024-55033. PMID: 15456760, DOI: 10.1074/jbc.m408886200.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesCell DifferentiationCell MembraneCell NucleusChromatin ImmunoprecipitationCREB-Binding ProteinDeoxyribonuclease IDNADNA PrimersDNA, ComplementaryDNA-Binding ProteinsErythrocytesErythroid-Specific DNA-Binding FactorsEthidiumExonsGATA1 Transcription FactorGenes, ReporterHeLa CellsHumansImmunoprecipitationIntronsK562 CellsLuciferasesModels, GeneticMolecular Sequence DataMutationNuclear ProteinsPlasmidsPromoter Regions, GeneticSpectrinTemperatureTrans-ActivatorsTranscription FactorsTransfectionConceptsErythroid-specific expressionAlpha-spectrin geneGATA-1 sitesCore promoterDNase I hypersensitive sitesElectrophoretic mobility shift assaysChromatin immunoprecipitation assaysMobility shift assaysΑ-spectrin geneThymidine kinase promoterPositive regulatory elementHigh-level expressionGenomic orientationErythroid promoterGATA-1Membrane proteinsHypersensitive sitesImmunoprecipitation assaysRegulatory elementsSequence downstreamShift assaysErythroid differentiationTransfection assaysEnhancer activityReporter gene
2002
Erythroid Expression of the Human α-Spectrin Gene Promoter Is Mediated by GATA-1- and NF-E2-binding Proteins*
Boulanger L, Sabatino DE, Wong EY, Cline AP, Garrett LJ, Garbarz M, Dhermy D, Bodine DM, Gallagher PG. Erythroid Expression of the Human α-Spectrin Gene Promoter Is Mediated by GATA-1- and NF-E2-binding Proteins*. Journal Of Biological Chemistry 2002, 277: 41563-41570. PMID: 12196550, DOI: 10.1074/jbc.m208184200.Peer-Reviewed Original ResearchMeSH Keywords5' Flanking RegionAnimalsBase SequenceBinding SitesDNA, ComplementaryDNA-Binding ProteinsErythroid Precursor CellsErythroid-Specific DNA-Binding FactorsErythropoiesisGATA1 Transcription FactorHeLa CellsHumansK562 CellsMiceMice, TransgenicMolecular Sequence DataNF-E2 Transcription FactorNF-E2 Transcription Factor, p45 SubunitPromoter Regions, GeneticSpectrinTranscription FactorsConceptsGene promoterGATA-1Reporter genePromoter/reporter plasmidsAlpha-spectrinGel mobility shift assaysErythroid-specific expressionFull promoter activityAlpha-spectrin geneMobility shift assaysErythroid progenitor cellsHuman tissue culture cell linesTissue culture cell linesAdult reticulocytesErythroid promoterNonerythroid tissuesMembrane proteinsLow-level expressionRegulatory elementsShift assaysErythroid expressionCell shapeDNase IErythroid cellsPromoter activity
2000
The human ankyrin-1 gene is selectively transcribed in erythroid cell lines despite the presence of a housekeeping-like promoter
Gallagher P, Romana M, Tse W, Lux S, Forget B. The human ankyrin-1 gene is selectively transcribed in erythroid cell lines despite the presence of a housekeeping-like promoter. Blood 2000, 96: 1136-1143. DOI: 10.1182/blood.v96.3.1136.Peer-Reviewed Original ResearchHuman ankyrin-1 geneGATA-1Ankyrin-1 geneErythroid promoterPromoter/reporter plasmidsMultiple transcription initiation sitesElectrophoretic mobility shift assaysHousekeeping gene promoterRegulation of genesCCAAT consensus sequencesTranscription initiation siteMobility shift assaysReporter gene expressionGATA-1 sitesFlanking genomic DNAErythroid cell linesAntibody supershift experimentsCell linesErythrocyte membrane proteinsTissue culture cell linesCACCC siteSp1 sitesMembrane proteinsPromoter sequencesAnkyrin geneThe human ankyrin-1 gene is selectively transcribed in erythroid cell lines despite the presence of a housekeeping-like promoter.
Gallagher P, Romana M, Tse W, Lux S, Forget B. The human ankyrin-1 gene is selectively transcribed in erythroid cell lines despite the presence of a housekeeping-like promoter. Blood 2000, 96: 1136-43. PMID: 10910934, DOI: 10.1182/blood.v96.3.1136.015k48_1136_1143.Peer-Reviewed Original ResearchConceptsHuman ankyrin-1 geneGATA-1Ankyrin-1 geneErythroid promoterPromoter/reporter plasmidsMultiple transcription initiation sitesElectrophoretic mobility shift assaysHousekeeping gene promoterRegulation of genesCCAAT consensus sequencesTranscription initiation siteMobility shift assaysReporter gene expressionGATA-1 sitesErythroid cell linesAntibody supershift experimentsCell linesErythrocyte membrane proteinsTissue culture cell linesCACCC siteSp1 sitesMembrane proteinsPromoter sequencesAnkyrin geneHTF island
1999
A Human β-Spectrin Gene Promoter Directs High Level Expression in Erythroid but Not Muscle or Neural Cells*
Gallagher P, Sabatino D, Romana M, Cline A, Garrett L, Bodine D, Forget B. A Human β-Spectrin Gene Promoter Directs High Level Expression in Erythroid but Not Muscle or Neural Cells*. Journal Of Biological Chemistry 1999, 274: 6062-6073. PMID: 10037687, DOI: 10.1074/jbc.274.10.6062.Peer-Reviewed Original ResearchConceptsBeta-spectrin geneGene promoterHigh-level expressionGATA-1Regulatory elementsReporter geneErythroid tissuesPromoter/reporter plasmidsGel mobility shift assaysLevel expressionGATA-1 motifsFull promoter activityTissue-specific expressionMobility shift assaysAdditional regulatory elementsErythrocyte membrane proteinsHuman tissue culture cell linesTissue culture cell linesErythroid promoterMembrane proteinsShift assaysBeta spectrinHeterologous cellsCell shapeDNase I
1998
An Alternate Promoter Directs Expression of a Truncated, Muscle-specific Isoform of the Human Ankyrin 1 Gene*
Gallagher P, Forget B. An Alternate Promoter Directs Expression of a Truncated, Muscle-specific Isoform of the Human Ankyrin 1 Gene*. Journal Of Biological Chemistry 1998, 273: 1339-1348. PMID: 9430667, DOI: 10.1074/jbc.273.3.1339.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceAnkyrinsBase SequenceCloning, MolecularDNA, ComplementaryErythroid Precursor CellsExonsGene Expression RegulationHumansMolecular Sequence DataMuscle, SkeletalMusclesMyocardiumMyoD ProteinPromoter Regions, GeneticRecombinant ProteinsTranscriptional ActivationConceptsKilobase pairsMuscle cDNADeduced amino acid sequenceCorresponding chromosomal geneHydrophobic NH2 terminusCultured C2C12 muscle cellsHuman ankyrin-1 geneSkeletal muscle cDNADNA-protein interactionsE-box consensusAmino acid sequenceK562 cellsMuscle-specific isoformPromoter directs expressionC2C12 muscle cellsAnkyrin-1 geneReporter gene plasmidHigh-level expressionNorthern blot analysisErythroid genesErythrocyte membrane proteinsSingle Sp1Erythroid promoterAlternative splicingRich promoter