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 ResearchMeSH KeywordsBeta-GlobinsErythropoiesisGATA1 Transcription FactorGene Expression RegulationHumansRNA Polymerase IIRNA-Binding ProteinsTranscription FactorsTranscription, GeneticConceptsFetal 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
2019
A Unique Epigenomic Landscape Defines Human Erythropoiesis
Schulz VP, Yan H, Lezon-Geyda K, An X, Hale J, Hillyer CD, Mohandas N, Gallagher PG. A Unique Epigenomic Landscape Defines Human Erythropoiesis. Cell Reports 2019, 28: 2996-3009.e7. PMID: 31509757, PMCID: PMC6863094, DOI: 10.1016/j.celrep.2019.08.020.Peer-Reviewed Original ResearchMeSH KeywordsChromatinChromatin Assembly and DisassemblyDNA MethylationEpigenesis, GeneticErythroid CellsErythropoiesisGene Expression ProfilingGene Expression RegulationHematologic DiseasesHematopoietic Stem CellsHumansMultigene FamilyPolymorphism, Single NucleotideRegulatory Sequences, Nucleic AcidTranscriptomeConceptsChromatin accessibilityDNA methylationHuman erythropoiesisStage-specific gene regulationErythroid cellsPrimary human erythroid cellsChromatin state dynamicsCell typesCis-regulatory elementsGenome-wide studiesSpecialized cell typesHuman erythroid cellsCell phenotypic variationNonhematopoietic cell typesChromatin primingErythroid genesEpigenomic landscapeGene regulationMammalian erythropoiesisPhenotypic variationTranscriptome dataOrganismal needsRegulation of erythropoiesisNonpromoter sitesGene expression
2018
Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs.
Kim ST, Choi JY, Lainez B, Schulz VP, Karas DE, Baum ED, Setlur J, Gallagher PG, Craft J. Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs. The Journal Of Immunology 2018, 201: 1359-1372. PMID: 30030323, PMCID: PMC6112860, DOI: 10.4049/jimmunol.1701217.Peer-Reviewed Original ResearchConceptsMemory B cellsHumoral recall responsesB cell folliclesT cell subsetsB cellsTfh cellsCell subsetsRecall responsesT cellsInhibitory receptor PD-1Follicular helper T cellsGerminal center B-cell maturationIL-21 secretionChemokine receptor expressionReceptor PD-1Helper T cellsT cell zonesPrimary immune responseChemokine receptor CXCR5Transcription factor Bcl6B cell maturationTonsillar CD4IL-10IL-21PD-1
2017
STAT4 and T-bet control follicular helper T cell development in viral infections
Weinstein JS, Laidlaw BJ, Lu Y, Wang JK, Schulz VP, Li N, Herman EI, Kaech SM, Gallagher PG, Craft J. STAT4 and T-bet control follicular helper T cell development in viral infections. Journal Of Experimental Medicine 2017, 215: 337-355. PMID: 29212666, PMCID: PMC5748849, DOI: 10.1084/jem.20170457.Peer-Reviewed Original ResearchConceptsIL-21Tfh cellsT-betViral infectionFollicular helper T cellsHelper T cell developmentAcute viral infectionIFN-γ productionHelper T cellsGerminal center B cell survivalB cell survivalT cell developmentIL-4Viral challengeIL-9T cellsImmunoglobulin isotypesIFNSoluble factorsGC responseInfectionGC reactionSTAT4BCL6Cell survival
2016
Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation
Li Y, Schulz VP, Deng C, Li G, Shen Y, Tusi BK, Ma G, Stees J, Qiu Y, Steiner LA, Zhou L, Zhao K, Bungert J, Gallagher PG, Huang S. Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation. Nucleic Acids Research 2016, 44: 7173-7188. PMID: 27141965, PMCID: PMC5009724, DOI: 10.1093/nar/gkw327.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, NuclearCell LineageCells, CulturedChromatinChromatin Assembly and DisassemblyChromatin ImmunoprecipitationErythroblastsErythrocyte CountErythrocytesErythropoiesisFemaleGene Expression RegulationHemoglobinsHistone-Lysine N-MethyltransferaseHistonesHumansLysineMaleMethylationMiceMice, KnockoutMicrococcal NucleaseMultiprotein ComplexesNerve Tissue ProteinsPromoter Regions, GeneticSpleenTranscription FactorsUpstream Stimulatory FactorsConceptsNURF complexChromatin dynamicsErythroid genesLineage commitmentAdult β-globin geneErythroid gene promotersErythroid lineage differentiationCell context-dependent mannerErythroid lineage commitmentChromatin structural alterationsContext-dependent mannerΒ-globin geneChromatin architectureEnhancer accessibilityChromatin accessibilityNucleosome repositioningTranscription regulationChromatin structureH3K4 methylationGene regulationComplex occupancyMammalian cellsGene activationGene transcriptionLineage differentiation
2014
Isolation and transcriptome analyses of human erythroid progenitors: BFU-E and CFU-E
Li J, Hale J, Bhagia P, Xue F, Chen L, Jaffray J, Yan H, Lane J, Gallagher PG, Mohandas N, Liu J, An X. Isolation and transcriptome analyses of human erythroid progenitors: BFU-E and CFU-E. Blood 2014, 124: 3636-3645. PMID: 25339359, PMCID: PMC4256913, DOI: 10.1182/blood-2014-07-588806.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, DifferentiationCell SeparationErythroid Precursor CellsErythropoiesisErythropoietinFemaleGene Expression RegulationHumansMaleTranscriptomeConceptsHuman BFUProgenitor populationsErythroid progenitorsDistinct progenitor populationsColony-forming unit-erythroid (CFU-E) cellsCFU-E cellsCFU-E coloniesCFU-E progenitorsHuman erythroid progenitorsUnit erythroid cellsColony assayErythroid cell culturesErythroid progenitor populationsTranscriptome analysisUnique transcriptomeStem cell factorCell culturesBioinformatics analysisHuman erythropoiesisFlow cytometry-based strategyMolecular characterizationBFU-E coloniesDifferentiation stagePrimary cellsCell factorGlobal transcriptome analyses of human and murine terminal erythroid differentiation
An X, Schulz VP, Li J, Wu K, Liu J, Xue F, Hu J, Mohandas N, Gallagher PG. Global transcriptome analyses of human and murine terminal erythroid differentiation. Blood 2014, 123: 3466-3477. PMID: 24637361, PMCID: PMC4041167, DOI: 10.1182/blood-2014-01-548305.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationErythroid differentiationGene expressionMurine terminal erythroid differentiationStage-specific transcriptomesDifferentiation stageGlobal transcriptome analysisStage-specific patternsRNA sequencing analysisGene expression profilesDistinct developmental stagesMurine transcriptomesFluorescence-activated cell sortingTranscriptional spaceErythroid developmentMurine erythroblastsTranscriptome analysisUnique transcriptomeBioinformatics analysisPerturbed erythropoiesisTranscriptomeExpression profilesErythroid disordersDevelopmental stagesSequencing analysis
2013
USF1 and hSET1A Mediated Epigenetic Modifications Regulate Lineage Differentiation and HoxB4 Transcription
Deng C, Li Y, Liang S, Cui K, Salz T, Yang H, Tang Z, Gallagher PG, Qiu Y, Roeder R, Zhao K, Bungert J, Huang S. USF1 and hSET1A Mediated Epigenetic Modifications Regulate Lineage Differentiation and HoxB4 Transcription. PLOS Genetics 2013, 9: e1003524. PMID: 23754954, PMCID: PMC3675019, DOI: 10.1371/journal.pgen.1003524.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Transcription FactorsCell DifferentiationCell LineageEmbryonic Stem CellsEpigenesis, GeneticGene Expression RegulationHistone-Lysine N-MethyltransferaseHomeodomain ProteinsHumansK562 CellsMesodermMethyltransferasesProto-Oncogene ProteinsT-Cell Acute Lymphocytic Leukemia Protein 1Transcription FactorsTranscriptional ActivationUpstream Stimulatory FactorsConceptsEmbryonic stem cellsLineage differentiationTrithorax complexesHoxb4 genesMethyltransferase complexTranscription preinitiation complex assemblyHistone H3K4 methyltransferase complexRNA interference-mediated knockdownBivalent chromatin domainsH3K4 methyltransferase complexUndifferentiated embryonic stem cellsPreinitiation complex assemblyHistone methyltransferase complexTranscription factor USF1H3K4 methyltransferase activityHematopoietic stem/progenitor cellsHematopoietic cell populationsStem/progenitor cellsDPY-30HOXB4 promoterMesoderm specificationChromatin domainsMesoderm differentiationH3K4me3 modificationHematopoietic transitionIdentification of Biologically Relevant Enhancers in Human Erythroid Cells*
Su MY, Steiner LA, Bogardus H, Mishra T, Schulz VP, Hardison RC, Gallagher PG. Identification of Biologically Relevant Enhancers in Human Erythroid Cells*. Journal Of Biological Chemistry 2013, 288: 8433-8444. PMID: 23341446, PMCID: PMC3605659, DOI: 10.1074/jbc.m112.413260.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBasic Helix-Loop-Helix Transcription FactorsCells, CulturedChromatinChromatin ImmunoprecipitationConserved SequenceE1A-Associated p300 ProteinEnhancer Elements, GeneticErythroid CellsGATA1 Transcription FactorGene Expression RegulationGenes, ReporterHigh-Throughput Nucleotide SequencingHumansKruppel-Like Transcription FactorsLuciferases, FireflyMolecular Sequence AnnotationNF-E2 Transcription Factor, p45 SubunitOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotidePromoter Regions, GeneticProtein BindingProto-Oncogene ProteinsRNA, MessengerSequence Analysis, DNAT-Cell Acute Lymphocytic Leukemia Protein 1TranscriptomeConceptsHuman erythroid cellsCandidate enhancersTranscriptional start siteErythroid cellsTranscription factorsGenome-wide association study catalogCell type-specific enhancersPrimary human erythroid cellsRegulation of programsGenome-wide mapsErythroid transcription factorsErythroid cell developmentSpecialized cell typesIdentification of enhancersGene expression analysisErythroid traitsMinimal conservationChromatin immunoprecipitationModerate conservationStart siteRelevant enhancersCellular developmentGenetic lociExpression analysisReporter gene
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
2009
Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes
Steiner LA, Maksimova Y, Schulz V, Wong C, Raha D, Mahajan MC, Weissman SM, Gallagher PG. Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes. Molecular And Cellular Biology 2009, 29: 5399-5412. PMID: 19687298, PMCID: PMC2756878, DOI: 10.1128/mcb.00777-09.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Transcription FactorsChromatinErythrocyte MembraneErythrocytesGATA1 Transcription FactorGene Expression RegulationHeLa CellsHistone DeacetylasesHumansMembrane ProteinsNF-E2 Transcription Factor, p45 SubunitNuclear ProteinsProto-Oncogene ProteinsRepressor ProteinsT-Cell Acute Lymphocytic Leukemia Protein 1Transcription FactorsConceptsErythrocyte membrane protein genesMembrane protein geneNF-E2 bindingGATA-1Protein geneChromatin architectureFOG-1Nonerythroid cellsBinding motifDynamic chromatin architectureHistone H3 trimethylationNF-E2Numerous candidate regionsTranscription factor bindingGATA-1 bindingTranscriptional start siteComplex genetic lociParallel DNA sequencingGenomic organizationLocus structureLysine 4H3 trimethylationGene regulationChromatin immunoprecipitationStart site
2008
An insulator with barrier-element activity promotes α-spectrin gene expression in erythroid cells
Gallagher PG, Nilson DG, Steiner LA, Maksimova YD, Lin JY, Bodine DM. An insulator with barrier-element activity promotes α-spectrin gene expression in erythroid cells. Blood 2008, 113: 1547-1554. PMID: 19008453, PMCID: PMC2644083, DOI: 10.1182/blood-2008-06-164954.Peer-Reviewed Original ResearchConceptsIntron 1Erythroid cellsErythrocyte membrane protein genesExon 1Chicken HS4 insulatorGamma-globin proteinChromatin immunoprecipitation assaysEarly erythroid developmentMembrane protein geneAlpha-spectrin geneTissue-specific expressionMembrane biogenesisErythroid developmentGlobin genesHS4 insulatorImmunoprecipitation assaysProtein geneReporter geneGene expressionDevelopmental stagesGenesPromoterAdult erythrocytesExpressionSpectrin
2007
Population analysis of the alpha hemoglobin stabilizing protein (AHSP) gene identifies sequence variants that alter expression and function
dos Santos CO, Zhou S, Secolin R, Wang X, Cunha AF, Higgs DR, Kwiatkowski JL, Thein SL, Gallagher PG, Costa FF, Weiss MJ. Population analysis of the alpha hemoglobin stabilizing protein (AHSP) gene identifies sequence variants that alter expression and function. American Journal Of Hematology 2007, 83: 103-108. PMID: 17874450, DOI: 10.1002/ajh.21041.Peer-Reviewed Original ResearchNovel role for EKLF in megakaryocyte lineage commitment
Frontelo P, Manwani D, Galdass M, Karsunky H, Lohmann F, Gallagher PG, Bieker JJ. Novel role for EKLF in megakaryocyte lineage commitment. Blood 2007, 110: 3871-3880. PMID: 17715392, PMCID: PMC2190608, DOI: 10.1182/blood-2007-03-082065.Peer-Reviewed Original ResearchConceptsErythroid gene regulationKrüppel-like factorMegakaryocyte-erythroid progenitorsFormation of megakaryocytesGene regulationTranscriptional regulatorsLineage commitmentTranscription factorsHematopoietic differentiationErythroid differentiationCommon progenitorExpression profilingErythroid cellsEKLFMegakaryocyte lineageNovel roleMolecular analysisLineagesMessage levelsFunction studiesMegakaryocytesProgenitorsDifferentiationRepressionGenes
2006
Alterations in Expression and Chromatin Configuration of the Alpha Hemoglobin-Stabilizing Protein Gene in Erythroid Krüppel-Like Factor-Deficient Mice
Pilon AM, Nilson DG, Zhou D, Sangerman J, Townes TM, Bodine DM, Gallagher PG. Alterations in Expression and Chromatin Configuration of the Alpha Hemoglobin-Stabilizing Protein Gene in Erythroid Krüppel-Like Factor-Deficient Mice. Molecular And Cellular Biology 2006, 26: 4368-4377. PMID: 16705186, PMCID: PMC1489081, DOI: 10.1128/mcb.02216-05.Peer-Reviewed Original ResearchConceptsErythroid Krüppel-like factorAlpha-hemoglobin-stabilizing proteinWild-type chromatinAHSP promoterCACCC siteBeta-globin gene transcriptionDNase I hypersensitive sitesLocal chromatin structureZinc finger proteinBeta-globin promoterKrüppel-like factorMobility shift assaysBeta-globin geneErythroid genesCACCC sequenceChromatin modulatorsFinger proteinChromatin structureSubtractive hybridizationChromatin statusCACCC boxTranscription factorsProtein geneChromatin configurationHypersensitive sitesMajor erythrocyte membrane protein genes in EKLF-deficient mice
Nilson DG, Sabatino DE, Bodine DM, Gallagher PG. Major erythrocyte membrane protein genes in EKLF-deficient mice. Experimental Hematology 2006, 34: 705-712. PMID: 16728274, DOI: 10.1016/j.exphem.2006.02.018.Peer-Reviewed Original ResearchConceptsErythrocyte membrane protein genesMembrane protein geneWild-type backgroundBand 3 geneProtein geneErythroid Krüppel-like factorGamma-globinGamma-globin mRNA levelsLevel of transcriptionGamma-globin expressionFull transcriptional activityKrüppel-like factorBeta-spectrin geneBand 3 mRNAGamma-globin mRNABeta-globin geneSteady-state mRNA levelsEmbryonic lethalityMRNA levelsEKLFAnkyrin promoterMembrane genesTranscriptional activityGlobin chain imbalanceErythroid cells
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 spectrinRegulation of erythrocyte membrane protein gene expression
Gallagher PG. Regulation of erythrocyte membrane protein gene expression. Current Opinion In Hematology 2003, 10: 115-122. PMID: 12579036, DOI: 10.1097/00062752-200303000-00003.Peer-Reviewed Original ResearchConceptsProtein gene expressionGene productsGene expressionCell typesErythroid-specific genesMultiple protein isoformsStage-specific functionsDevelopmental stage-specific functionsDifferent gene productsTissue-specific promotersSame gene productDifferent cell typesIsoform diversityGene regulationFunctional diversityNonerythroid cellsMultifunctional proteinProtein isoformsRegulatory elementsAlternate polyadenylationAlternate splicingMembrane assemblyRegulated expressionRelated genesHomologous family
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: 1136-43. 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