2024
HEXIM1 Regulates Early Erythropoiesis and Participates in Multiple Complexes in Erythroid Cells
Rahman N, Abid D, Lv X, Murphy K, Getman M, McGrath K, Gallagher P, Narla M, Blanc L, Palis J, Mello S, Steiner L. HEXIM1 Regulates Early Erythropoiesis and Participates in Multiple Complexes in Erythroid Cells. Blood 2024, 144: 536. DOI: 10.1182/blood-2024-209259.Peer-Reviewed Original ResearchRNA polymerase IIErythroid gene expressionGene expressionTerminal erythroid maturationEarly erythropoiesisErythroid cellsErythroid maturationRegulation of gene expressionProgenitor cellsImpaired erythroid differentiationRNAPII pausingGenomic contextPolymerase IIRepress transcriptionSteady-state erythropoiesisErythroid progenitor cellsCD34+ HSPCsRegulatory domainBinding partnersErythropoiesis in vivoBlood cell countColony-forming cellsLow red blood cell countSubnuclear bodiesErythroid progenitor differentiation
2021
Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency
Wang Y, Li W, Schulz VP, Zhao H, Qu X, Qi Q, Cheng Y, Guo X, Zhang S, Wei X, Liu D, Yazdanbakhsh K, Hillyer CD, Mohandas N, Chen L, Gallagher PG, An X. Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency. Blood 2021, 138: 1615-1627. PMID: 34036344, PMCID: PMC8554652, DOI: 10.1182/blood.2020007401.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationChromatin condensationErythroid differentiationHuman erythroid cellsAcetylation of H4RNA sequencing analysisEnucleation of erythroblastsGroup of enzymesLate-stage erythroblastsErythroid cell culturesHDAC family membersActivation of p53Short hairpin RNAChromatin accessibilityATAC-seqMammalian erythropoiesisH4 deacetylationNonhistone proteinsH4 acetylationDiverse functionsHDAC inhibitor treatmentHuman erythropoiesisKnockdown of HDAC5Erythroid cellsGene expressionComprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis
Yan H, Ali A, Blanc L, Narla A, Lane JM, Gao E, Papoin J, Hale J, Hillyer CD, Taylor N, Gallagher PG, Raza A, Kinet S, Mohandas N. Comprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis. American Journal Of Hematology 2021, 96: 1064-1076. PMID: 34021930, PMCID: PMC8355124, DOI: 10.1002/ajh.26247.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationErythroid differentiationHuman erythropoiesisErythroid cellsErythroid progenitorsPrimary bone marrow cellsPrimary erythroid cellsDisorders of erythropoiesisStage-specific defectsErythroid progenitor cellsFunctional insightsProgenitor stageProgenitor populationsHuman bone marrowBone marrowFactor responsivenessNormal erythropoiesisProgenitor cellsBone marrow cellsDiscrete populationsColony assayFlow cytometry-based techniqueDifferentiationProliferative capacityEarly population
2020
Comprehensive proteomic analysis of murine terminal erythroid differentiation
Gautier EF, Leduc M, Ladli M, Schulz VP, Lefèvre C, Boussaid I, Fontenay M, Lacombe C, Verdier F, Guillonneau F, Hillyer CD, Mohandas N, Gallagher PG, Mayeux P. Comprehensive proteomic analysis of murine terminal erythroid differentiation. Blood Advances 2020, 4: 1464-1477. PMID: 32282884, PMCID: PMC7160260, DOI: 10.1182/bloodadvances.2020001652.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationErythroid differentiationProteomic dataMurine terminal erythroid differentiationTerminal differentiationOverall cellular contentComprehensive proteomic dataComprehensive proteomic analysisMurine erythroid cellsTerminal differentiation processMost biologic processesProteome levelComparison of murineHuman proteomeProteomic analysisTranscriptomic changesChromatin condensationProteomeErythroid cellsFundamental mechanismsRed cell disordersDifferentiation processErythroid progenitorsFriend erythroleukemiaCellular model
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 expressionIdentification and transcriptome analysis of erythroblastic island macrophages
Li W, Wang Y, Zhao H, Zhang H, Xu Y, Wang S, Guo X, Huang Y, Zhang S, Han Y, Wu X, Rice CM, Huang G, Gallagher PG, Mendelson A, Yazdanbakhsh K, Liu J, Chen L, An X. Identification and transcriptome analysis of erythroblastic island macrophages. Blood 2019, 134: 480-491. PMID: 31101625, PMCID: PMC6676133, DOI: 10.1182/blood.2019000430.Peer-Reviewed Original ResearchConceptsErythroblastic islandsEBI macrophagesErythroid cellsErythroblastic island macrophagesGene expression profilesTranscriptome analysisNonerythroid cellsMacrophage functionHematopoietic nicheExpression profilesSpecialized functionsCentral macrophageKnockin mouse modelFlow cytometry analysisEpoRKey moleculesIron recyclingBone marrowCytometry analysisFetal liverNicheEfficient erythropoiesisErythropoiesisIron sourceImportant resource
2018
Altered Splicing from a Mutated Alternate Branch Point Is Common in Severe Alpha-Spectrin Linked Inherited Anemia
Lezon-Geyda K, Schulz V, Maksimova Y, Gallagher P. Altered Splicing from a Mutated Alternate Branch Point Is Common in Severe Alpha-Spectrin Linked Inherited Anemia. Blood 2018, 132: 503. DOI: 10.1182/blood-2018-99-117752.Peer-Reviewed Original ResearchMRNA transcriptsTermination codonK562 cellsMinigene assayIntron 30Precise genetic basisAcceptor sitesInsertion/deletion mutationsHereditary pyropoikilocytosisWhole-genome sequencingNMD inhibitorsAcceptor splice siteDiagnostic gene panelsGenome databaseMRNA splicingWild-type minigeneConsensus sitesAltered splicingExon 31Genetic basisTranscript productionErythroid cellsGene manipulationGenetic analysisWT background
2017
Distinct roles for TET family proteins in regulating human erythropoiesis
Yan H, Wang Y, Qu X, Li J, Hale J, Huang Y, An C, Papoin J, Guo X, Chen L, Kang Q, Li W, Schulz VP, Gallagher PG, Hillyer CD, Mohandas N, An X. Distinct roles for TET family proteins in regulating human erythropoiesis. Blood 2017, 129: 2002-2012. PMID: 28167661, PMCID: PMC5383871, DOI: 10.1182/blood-2016-08-736587.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromeErythroid differentiationHuman erythropoiesisErythroid progenitorsHuman erythroid differentiationTET family proteinsDistinct rolesKnockdown of TET2Terminal erythroid differentiationHuman erythroid cellsTET2 gene mutationsFamily proteinsTranslocation (TET) familyTET2 knockdownKnockdown experimentsErythroid cellsBiological processesDevelopment defectsTET3TET3 expressionOrthochromatic erythroblastsImpaired differentiationHuman CD34KnockdownTET2
2016
CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells
Steiner LA, Schulz V, Makismova Y, Lezon-Geyda K, Gallagher PG. CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells. PLOS ONE 2016, 11: e0155378. PMID: 27219007, PMCID: PMC4878738, DOI: 10.1371/journal.pone.0155378.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCCCTC-Binding FactorCells, CulturedChromatinChromatin ImmunoprecipitationErythroid CellsErythropoiesisGene Expression ProfilingHematopoietic Stem CellsHigh-Throughput Nucleotide SequencingHumansK562 CellsNuclear ProteinsPromoter Regions, GeneticProtein BindingProtein Interaction MapsRepressor ProteinsSequence Analysis, RNAConceptsPrimary human erythroid cellsRepressive chromatin domainsHuman erythroid cellsChromatin domainsErythroid cellsChromatin architectureGene promoterGene expressionPrimary human hematopoietic stemCell type-specific mannerCritical cellular processesSites of CTCFGenome-wide dataHigh-throughput sequencingMRNA transcriptome analysisHuman hematopoietic stemRepressive chromatinCohesin sitesProtein occupancyInsulator functionRepressive domainsTranscriptional regulationCTCF sitesDomain architectureRelated gene expression
2015
The Histone Methyltransferase Setd8 Is Essential for Mammalian Erythropoiesis
Malik J, Getman M, Lillis J, Gallagher P, Steiner L. The Histone Methyltransferase Setd8 Is Essential for Mammalian Erythropoiesis. Blood 2015, 126: 3577. DOI: 10.1182/blood.v126.23.3577.3577.Peer-Reviewed Original ResearchCell cycle progressionNuclear condensationTranscriptional regulationMammalian erythropoiesisErythroid maturationGATA2 expressionErythroid cellsCycle progressionHistone H4 lysine 20Sole histone methyltransferaseGFP fusion proteinH4 lysine 20Histone methyltransferase Setd8Erythroid transcription factorsErythroid-specific genesEarly embryonic lethalityGlobal transcriptome analysisDNA damage responseMajority of transcriptsRNA-seq analysisCell cycle checkpointsKey regulatory regionsCommitted erythroid progenitorsErythro-myeloid progenitorsPrimary human erythroblasts
2013
Enhancers and Super Enhancers Are Associated With Genes That Control Phenotypic Traits In Primary Human Erythroid Cells
Schulz V, Lezon-Geyda K, Maksimova Y, Gallagher P. Enhancers and Super Enhancers Are Associated With Genes That Control Phenotypic Traits In Primary Human Erythroid Cells. Blood 2013, 122: 1200. DOI: 10.1182/blood.v122.21.1200.1200.Peer-Reviewed Original ResearchTranscriptional start siteRegulation of programsSuper enhancersErythroid cellsGene expressionErythroid enhancerTF motifsTranscription factorsHistone H3 lysine 4 monomethylationSpecific enhancersH3K27ac modificationGWAS catalogGene locusHistone H3 lysine 27 acetylationCell type-specific enhancersPrimary human erythroid cellsH3 lysine 27 acetylationAlpha-globin gene clusterDisease-associated genetic variantsGenome-wide mapsNHGRI GWAS catalogSubset of enhancersHundreds of kilobasesLysine 27 acetylationSpecialized cell typesIdentification 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
2012
Identification of Biologicaly Relevant Enhancers in Human Erythroid Cells
Su M, Steiner L, Bogardus H, Schulz V, Hardison R, Gallagher P. Identification of Biologicaly Relevant Enhancers in Human Erythroid Cells. Blood 2012, 120: 368. DOI: 10.1182/blood.v120.21.368.368.Peer-Reviewed Original ResearchTranscriptional start siteHuman erythroid cellsCell type-specific enhancersErythroid transcription factorsErythroid-specific genesTranscription factorsErythroid cellsCandidate enhancersSpecific enhancersSignificant enrichmentGene expressionPrimary human erythroid cellsRegulation of programsDisease-associated genetic variantsGenome-wide mapsHundreds of kilobasesSpecialized cell typesTranscription factor sitesKb of genesGene expression analysisParallel gene expression analysisGenomic vicinityGenomic methodologiesEvolutionary analysisHigh conservation
2011
Unbiased Identification of Functional Barrier Insulators in Primary Human Erythroid Cells,
Steiner L, Schulz V, Maksimova Y, Seidel N, Bodine D, Gallagher P. Unbiased Identification of Functional Barrier Insulators in Primary Human Erythroid Cells,. Blood 2011, 118: 3385. DOI: 10.1182/blood.v118.21.3385.3385.Peer-Reviewed Original ResearchHuman erythroid cellsPrimary human erythroid cellsPosition-effect variegationInsulator functionErythroid cellsCpG methylationBarrier insulatorsGene promoterCell type-specific gene expressionRepressive histone mark H3K27me3Unbiased identificationParallel sequencingUpstream stimulatory factor proteinsCTCF ChIP-seqMethyl-Binding DomainGenome-wide bindingGenome-wide mapsRole of CTCFCell type-specific mannerGenome-wide scaleHistone mark H3K27me3Chicken erythroid cellsDirection of transcriptionMultiple regulatory proteinsChIP-seq studiesTransfusion-Dependent Alpha-Spectrin Deficient Hemolytic Anemia Due to Maternal Uniparental Disomy
Bogardus H, Schulz V, Maksimova Y, Miller B, Forget B, Gallagher P. Transfusion-Dependent Alpha-Spectrin Deficient Hemolytic Anemia Due to Maternal Uniparental Disomy. Blood 2011, 118: 1030. DOI: 10.1182/blood.v118.21.1030.1030.Peer-Reviewed Original ResearchAlpha-spectrin geneArray comparative genomic hybridizationGene locusGenomic DNANonsense mutationUniparental disomyDeleterious recessive mutationsEntire human genomeMaternal uniparental disomyCultured erythroid cellsParental genomic DNARegions of homozygosityHuman genomeSingle chromosomeComparative genomic hybridizationMolecular basisSNP dataSPTA1 geneHomozygous nonsense mutationChromosome 1Erythroid cellsGene regionPromoter regionRecessive mutationsAnemia phenotypeIntegrated Genome-Wide CTCF and CohesinSA1 Occupancy and Expression Analyses in Erythropoiesis
Schulz V, Steiner L, Maksimova Y, Gallagher P. Integrated Genome-Wide CTCF and CohesinSA1 Occupancy and Expression Analyses in Erythropoiesis. Blood 2011, 118: 1305. DOI: 10.1182/blood.v118.21.1305.1305.Peer-Reviewed Original ResearchSites of CTCFCTCF sitesCell-type specificIntergenic regionErythroid cellsChromatin domainsCohesin complexCell typesGene promoterRefSeq genesLong-range chromatin interactionsPrimary human erythroid cellsRepressive chromatin marksCell type-specific mannerDistal intergenic regionsMacromolecule catabolic processHigh-throughput sequencingHuman erythroid cellsMRNA transcriptome analysisChromatin marksChromatin interactionsChromosome segregationInduction of apoptosisCTCF bindingTranscriptional activatorPatterns 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
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 cellsGenesA Common Regulatory Signature Associated with Barrier Insulators in Human Primary Erythroid Cells
Steiner L, Maksimova Y, Schulz V, Gallagher P. A Common Regulatory Signature Associated with Barrier Insulators in Human Primary Erythroid Cells. Blood 2010, 116: 3868. DOI: 10.1182/blood.v116.21.3868.3868.Peer-Reviewed Original ResearchGenome-wide mapsPrimary erythroid cellsErythroid cellsProximal promoterChromatin domainsBarrier insulatorsChIP-seqRegulatory signaturesMammalian cellsGene promoterEnhancer-blocking insulator activityTissue-specific gene expressionUpstream stimulatory factor proteinsHeterochromatin-mediated geneGenome-wide occupancyRole of CTCFRecruitment of enzymesΒ-globin locusHistone methyltransferase activityHuman primary erythroid cellsSpecific transcription factorsChicken β-globin locusProximal promoter regionProtein CTCFChromatin boundariesDynamic CO-Localization of GATA1, NFE2, and EKLF and Changes in Gene Expression During Hematopoiesis
Steiner L, Schulz V, Maksimova Y, Mahajan M, Bodine D, Gallagher P. Dynamic CO-Localization of GATA1, NFE2, and EKLF and Changes in Gene Expression During Hematopoiesis. Blood 2010, 116: 741. DOI: 10.1182/blood.v116.21.741.741.Peer-Reviewed Original ResearchErythroid cellsGene expressionTranscription factorsProximal promoterCell type-specific gene expressionHuman beta-globin gene locusBeta-globin gene locusErythrocyte membrane protein genesErythroid-expressed genesGenome-wide scaleGlobin gene locusDNA-protein interactionsHuman primary erythroid cellsNF-E2Primary erythroid cellsMembrane protein geneSpecific gene expressionCritical regulatory elementsPrimary hematopoietic stemCommon regulatory siteUltrahigh-throughput sequencingLineage choiceChromatin immunoprecipitationCoordinated bindingEKLF