2023
HEXIM1 is an essential transcription regulator during human erythropoiesis
Lv X, Murphy K, Murphy Z, Getman M, Rahman N, Nakamura Y, Blanc L, Gallagher P, Palis J, Mohandas N, Steiner L. HEXIM1 is an essential transcription regulator during human erythropoiesis. Blood 2023, 142: 2198-2215. PMID: 37738561, PMCID: PMC10733840, DOI: 10.1182/blood.2022019495.Peer-Reviewed Original ResearchConceptsFetal globin expressionGene expressionGlobin expressionCycle progressionErythroid gene expressionBeta-globinBeta-globin locusGenome-wide profilingRNA polymerase II activityLong non-coding RNANon-coding RNAErythroid proliferationPolymerase II activityCell cycle progressionEssential transcription regulatorRNAPII activityRNAPII occupancyGlobin locusTranscription machineryTranscription regulatorsFetal globinRNAPIIFetal gene expressionHEXIM1Human erythropoiesis
2021
Regulation of RNA polymerase II activity is essential for terminal erythroid maturation
Murphy ZC, Murphy K, Myers J, Getman M, Couch T, Schulz VP, Lezon-Geyda K, Palumbo C, Yan H, Mohandas N, Gallagher PG, Steiner LA. Regulation of RNA polymerase II activity is essential for terminal erythroid maturation. Blood 2021, 138: 1740-1756. PMID: 34075391, PMCID: PMC8569412, DOI: 10.1182/blood.2020009903.Peer-Reviewed Original ResearchMeSH KeywordsCell LineChromatinErythroblastsErythroid CellsErythropoiesisGene Expression Regulation, DevelopmentalHistonesHumansRNA Polymerase IITranscription, GeneticConceptsRNA polymerase IIRNA polymerase II activityTerminal erythroid maturationPolymerase II activityPolymerase IIErythroid maturationHuman erythroblastsGene expressionTerminal maturationII activityStage-specific regulationHistone posttranslational modificationsTransposase-accessible chromatinErythroid-specific genesAccumulation of heterochromatinHigh-throughput sequencingLevel of transcriptionLate-stage erythroblastsEssential biologic processesAccessible chromatinHistone marksTranscription elongationChromatin structureTranscriptional repressionChromatin immunoprecipitation
2015
Pomalidomide reverses γ-globin silencing through the transcriptional reprogramming of adult hematopoietic progenitors
Dulmovits BM, Appiah-Kubi AO, Papoin J, Hale J, He M, Al-Abed Y, Didier S, Gould M, Husain-Krautter S, Singh SA, Chan KW, Vlachos A, Allen SL, Taylor N, Marambaud P, An X, Gallagher PG, Mohandas N, Lipton JM, Liu JM, Blanc L. Pomalidomide reverses γ-globin silencing through the transcriptional reprogramming of adult hematopoietic progenitors. Blood 2015, 127: 1481-1492. PMID: 26679864, PMCID: PMC4797024, DOI: 10.1182/blood-2015-09-667923.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnemia, Sickle CellBeta-GlobinsCarrier ProteinsErythroid Precursor CellsErythropoiesisFetal HemoglobinGamma-GlobinsGene Expression Regulation, DevelopmentalGenetic VectorsHematopoietic Stem CellsHistone DemethylasesHumansIkaros Transcription FactorKruppel-Like Transcription FactorsLentivirusMultiple MyelomaNeoplasm ProteinsNuclear ProteinsProteasome Endopeptidase ComplexRepressor ProteinsRNA InterferenceRNA, Small InterferingSOXD Transcription FactorsThalidomideTranscription, GeneticConceptsSickle cell anemiaCell anemiaΓ-globinThird-generation immunomodulatory drugAdult human erythroblastsMultiple myeloma patientsHematopoietic progenitorsΓ-globin levelsΓ-globin repressionCurrent therapeutic strategiesErythroid differentiation programFetal hemoglobinAdult hematopoietic progenitorsPomalidomide treatmentImmunomodulatory drugsMyeloma patientsTranscriptional reprogrammingFetal hemoglobin productionTranscription networksTherapeutic strategiesDifferentiation programPomalidomideHuman erythroblastsΒ-hemoglobinopathiesGenetic ablation
2011
Patterns of Histone H3 Lysine 27 Monomethylation and Erythroid Cell Type-specific Gene Expression*
Steiner LA, Schulz VP, Maksimova Y, Wong C, Gallagher PG. Patterns of Histone H3 Lysine 27 Monomethylation and Erythroid Cell Type-specific Gene Expression*. Journal Of Biological Chemistry 2011, 286: 39457-39465. PMID: 21937433, PMCID: PMC3234769, DOI: 10.1074/jbc.m111.243006.Peer-Reviewed Original ResearchConceptsTranscription start siteCell type-specific gene expressionGene expressionHistone modificationsType-specific gene expressionPost-translational histone modificationsHistone H3 lysine 27Numerous cellular processesH3 lysine 27Gene-specific patternsSpecific gene expressionContext-dependent mannerExpression array analysisChromatin signaturesGene bodiesH3K27 monomethylationActive genesActive transcriptionCellular processesChromatin immunoprecipitationIndividual genesLysine 27Start siteChip microarrayErythroid cells
2010
Functional Analysis of a Novel cis-Acting Regulatory Region within the Human Ankyrin Gene (ANK-1) Promoter
Laflamme K, Owen AN, Devlin EE, Yang MQ, Wong C, Steiner LA, Garrett LJ, Elnitski L, Gallagher PG, Bodine DM. Functional Analysis of a Novel cis-Acting Regulatory Region within the Human Ankyrin Gene (ANK-1) Promoter. Molecular And Cellular Biology 2010, 30: 3493-3502. PMID: 20479128, PMCID: PMC2897556, DOI: 10.1128/mcb.00119-10.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsAnimalsAnkyrinsBase SequenceBinding SitesCell-Free SystemConsensus SequenceDNADNA PrimersGene LibraryHumansIn Vitro TechniquesMiceMice, TransgenicMolecular Sequence DataPromoter Regions, GeneticRegulatory Sequences, Nucleic AcidSequence DeletionSequence Homology, Nucleic AcidTATA-Box Binding ProteinTranscription Factor TFIIDTranscription, GeneticConceptsCell-free transcriptionPromoter functionGene promoterDinucleotide deletionANK-1 geneNovel regulatory elementFunctional promoter sequencesNovel functional motifsTransgenic mouse assaysPreinitiation complexRegulatory sequencesPromoter sequencesRegulatory regionsRegulatory elementsFunctional motifsUntranslated regionWild typeFunctional analysisAdditional sequencesDegenerate sequencePromoterMutationsTranscriptionDeletionSequence
2008
Failure of Terminal Erythroid Differentiation in EKLF-Deficient Mice Is Associated with Cell Cycle Perturbation and Reduced Expression of E2F2
Pilon AM, Arcasoy MO, Dressman HK, Vayda SE, Maksimova YD, Sangerman JI, Gallagher PG, Bodine DM. Failure of Terminal Erythroid Differentiation in EKLF-Deficient Mice Is Associated with Cell Cycle Perturbation and Reduced Expression of E2F2. Molecular And Cellular Biology 2008, 28: 7394-7401. PMID: 18852285, PMCID: PMC2593440, DOI: 10.1128/mcb.01087-08.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CycleCell DifferentiationE2F2 Transcription FactorEmbryo, MammalianErythropoiesisGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Regulatory NetworksKruppel-Like Transcription FactorsLiverMiceMice, KnockoutOligonucleotide Array Sequence AnalysisPromoter Regions, GeneticStem CellsTranscription, GeneticConceptsErythroid Krüppel-like factorTerminal erythroid differentiationEarly erythroid progenitor cellsErythroid progenitor cellsErythroid differentiationChromatin modifiersProgenitor cellsKrüppel-like transcription factorsNetwork of genesCell cycle regulationChromatin immunoprecipitation analysisKrüppel-like factorCell cycle progressionFailure of erythropoiesisS phase transitionEarly progenitor cellsTranscriptional activatorCycle regulationTranscriptional profilingTranscription factorsTarget genesImmunoprecipitation analysisDNase IErythroid cellsCycle progression
2005
A 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
2003
Variegated Expression from the Murine Band 3 (AE1) Promoter in Transgenic Mice Is Associated with mRNA Transcript Initiation at Upstream Start Sites and Can Be Suppressed by the Addition of the Chicken β-Globin 5′ HS4 Insulator Element
Frazar TF, Weisbein JL, Anderson SM, Cline AP, Garrett LJ, Felsenfeld G, Gallagher PG, Bodine DM. Variegated Expression from the Murine Band 3 (AE1) Promoter in Transgenic Mice Is Associated with mRNA Transcript Initiation at Upstream Start Sites and Can Be Suppressed by the Addition of the Chicken β-Globin 5′ HS4 Insulator Element. Molecular And Cellular Biology 2003, 23: 4753-4763. PMID: 12832463, PMCID: PMC162203, DOI: 10.1128/mcb.23.14.4753-4763.2003.Peer-Reviewed Original ResearchConceptsStart siteGamma-globin mRNAUpstream start siteVariegated expressionInsulator elementsHuman gamma-globin geneGamma-globin proteinPosition-effect variegationGamma-globin geneErythroid-specific expressionHS4 insulator elementsBeta-globin clusterHigh steady-state levelsTransgenic mouse assaysErythrocyte membrane skeletonTransgenic miceTransgene copy numberTranscript initiationCytoplasmic domainTransmembrane proteinSteady-state levelsRNA transcriptionMembrane skeletonGene promoterBeta spectrin
2000
Long-term expression of γ-globin mRNA in mouse erythrocytes from retrovirus vectors containing the human γ-globin gene fused to the ankyrin-1 promoter
Sabatino D, Seidel N, Aviles-Mendoza G, Cline A, Anderson S, Gallagher P, Bodine D. Long-term expression of γ-globin mRNA in mouse erythrocytes from retrovirus vectors containing the human γ-globin gene fused to the ankyrin-1 promoter. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 13294-13299. PMID: 11069298, PMCID: PMC27218, DOI: 10.1073/pnas.230453097.Peer-Reviewed Original ResearchConceptsGlobin genesRetrovirus vectorHematopoietic stem cellsGene promoterHuman γ-globin genesMouse alpha-globin mRNACis-acting regulatory sequencesGlobin gene promoterMouse hematopoietic stem cellsΓ-globin geneGamma-globin geneAlpha-globin mRNAStem cellsMature red blood cellsNumber-dependent expressionIntact proviral sequencesΓ-globin mRNARegulatory sequencesLevel of expressionGlobin mRNARed cell disordersGenesPromoterThe 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 ResearchMeSH KeywordsAnkyrinsBase SequenceCell LineErythrocytesGene Expression RegulationHumansMolecular Sequence DataPromoter Regions, GeneticTranscription, GeneticConceptsHuman 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