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 ResearchConceptsRNA 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
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 expressionMKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation
Hu X, Liu ZZ, Chen X, Schulz VP, Kumar A, Hartman AA, Weinstein J, Johnston JF, Rodriguez EC, Eastman AE, Cheng J, Min L, Zhong M, Carroll C, Gallagher PG, Lu J, Schwartz M, King MC, Krause DS, Guo S. MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation. Nature Communications 2019, 10: 1695. PMID: 30979898, PMCID: PMC6461646, DOI: 10.1038/s41467-019-09636-6.Peer-Reviewed Original ResearchConceptsCell fate reprogrammingChromatin accessibilityActin cytoskeletonSomatic cell reprogrammingPluripotency transcription factorsGlobal chromatin accessibilityGenomic accessibilityCytoskeleton (LINC) complexCell reprogrammingCytoskeletal genesTranscription factorsReprogrammingPluripotencyChromatinCytoskeletonMKL1Unappreciated aspectPathwayNuclear volumeNucleoskeletonSUN2CellsActivationGenesExpression
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 expressionSetd1a 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
2013
Identification 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
A tissue-specific chromatin loop activates the erythroid ankyrin-1 promoter
Yocum AO, Steiner LA, Seidel NE, Cline AP, Rout ED, Lin JY, Wong C, Garrett LJ, Gallagher PG, Bodine DM. A tissue-specific chromatin loop activates the erythroid ankyrin-1 promoter. Blood 2012, 120: 3586-3593. PMID: 22968456, PMCID: PMC3482866, DOI: 10.1182/blood-2012-08-450262.Peer-Reviewed Original Research3' Untranslated Regions5' Untranslated RegionsAnimalsAnkyrinsBinding SitesCell Line, TumorChromatinDeoxyribonuclease IEnhancer Elements, GeneticHistonesHumansInsulator ElementsK562 CellsMiceMice, TransgenicNF-E2 Transcription Factor, p45 SubunitOrgan SpecificityPromoter Regions, GeneticProtein BindingProtein IsoformsSpherocytosis, Hereditary
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 cellsChromatin boundaries require functional collaboration between the hSET1 and NURF complexes
Li X, Wang S, Li Y, Deng C, Steiner LA, Xiao H, Wu C, Bungert J, Gallagher PG, Felsenfeld G, Qiu Y, Huang S. Chromatin boundaries require functional collaboration between the hSET1 and NURF complexes. Blood 2011, 118: 1386-1394. PMID: 21653943, PMCID: PMC3152501, DOI: 10.1182/blood-2010-11-319111.Peer-Reviewed Original ResearchConceptsErythroid genesInsulator sitesBarrier activityActive chromatin structureNucleosome remodeling activitiesChromatin barrier activityHistone H3K4 methyltransferaseChicken β-globinChromatin boundariesNURF complexChromatin structureInsulator functionNucleosome positioningMultiprotein complexesProtein complexesH3K4 methyltransferaseHS4 insulatorChromatin insulatorNURFH3K27me3 levelsLoci resultsLinker regionKnock-downΒ-globinFunctional collaboration
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
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
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 sites
2004
Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element
Zhou GP, Wong C, Su R, Crable SC, Anderson KP, Gallagher PG. Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element. Blood 2004, 103: 4302-4309. PMID: 14976052, DOI: 10.1182/blood-2003-01-0107.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsAcetylationBase SequenceCarcinoma, HepatocellularChromatinCloning, MolecularDNA-Binding ProteinsErythroid CellsHeLa CellsHumansK562 CellsMolecular Sequence DataPrecipitin TestsPromoter Regions, GeneticSp1 Transcription FactorSymportersTranscription Factor AP-2Transcription FactorsTranscription Initiation SiteConceptsDownstream promoter elementAP-2Gene promoterSp1 sitesK-Cl cotransportPromoter elementsKCC1 geneMammalian gene promotersElectrophoretic mobility shift assaysChromatin immunoprecipitation assaysFull promoter activityMobility shift assaysCore promoter regionReporter gene assayChloride cotransporter 1TATA boxImmunoprecipitation assaysInitiator elementShift assaysHeterologous cellsMutational analysisDNase IPromoter regionGenomic DNAPromoter activity