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
2013
The common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation
Harper SL, Sriswasdi S, Tang HY, Gaetani M, Gallagher PG, Speicher DW. The common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation. Blood 2013, 122: 3045-3053. PMID: 23974198, PMCID: PMC3811177, DOI: 10.1182/blood-2013-02-487702.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCross-Linking ReagentsElliptocytosis, HereditaryErythrocyte MembraneHumansModels, MolecularMolecular Sequence DataMutationProtein BindingProtein MultimerizationProtein StabilityProtein Structure, SecondaryProtein Structure, TertiaryRecombinant ProteinsSpectrinConceptsHereditary elliptocytosisMembrane destabilizationLarge conformational rearrangementsGel filtration analysisMembrane proteinsTetramer assemblyHereditary pyropoikilocytosisBiophysical analysisCommon hereditary elliptocytosisConformational rearrangementsDimer conformationHelical contentTetramerization siteFiltration analysisSpectrin tetramersNovel mechanismUnknown mechanismMutationsBinding assaysSpectrinChemical crosslinkingErythrocyte shapeTetramerErythrocyte membranesMembrane
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
Genome-wide ChIP-Seq reveals a dramatic shift in the binding of the transcription factor erythroid Kruppel-like factor during erythrocyte differentiation
Pilon AM, Ajay SS, Kumar SA, Steiner LA, Cherukuri PF, Wincovitch S, Anderson SM, Mullikin J, Gallagher P, Hardison R, Margulies E, Bodine D. Genome-wide ChIP-Seq reveals a dramatic shift in the binding of the transcription factor erythroid Kruppel-like factor during erythrocyte differentiation. Blood 2011, 118: e139-e148. PMID: 21900194, PMCID: PMC3208289, DOI: 10.1182/blood-2011-05-355107.Peer-Reviewed Original ResearchConceptsErythroid Kruppel-like factorKruppel-like factorChIP-seqTranscription factorsGenome-wide ChIP-seqProgenitor cellsMouse erythroid progenitor cellsCell cycle regulatory pathwaysErythroid transcription factorsGeneral cell growthRNA-seq analysisErythroid progenitor cellsTranscriptional activatorGATA factorsIntragenic regionsErythrocyte differentiationRegulatory pathwaysNuclear distributionPromoter regionParallel sequencingInteractomeDifferentiated erythroblastsCell growthTAL1Little overlap
2010
Genome-wide detection of a TFIID localization element from an initial human disease mutation
Yang MQ, Laflamme K, Gotea V, Joiner CH, Seidel NE, Wong C, Petrykowska HM, Lichtenberg J, Lee S, Welch L, Gallagher PG, Bodine DM, Elnitski L. Genome-wide detection of a TFIID localization element from an initial human disease mutation. Nucleic Acids Research 2010, 39: 2175-2187. PMID: 21071415, PMCID: PMC3064768, DOI: 10.1093/nar/gkq1035.Peer-Reviewed Original ResearchConceptsPromoter elementsPromoter motifsHuman promotersCore promoter motifsEukaryotic core promotersGenome-wide scalePre-initiation complexTranscription factor TFIIDGenome-wide detectionNovel promoter elementTranscription start siteHuman disease mutationsBasal promoter elementsFactor TFIIDTranscriptional machineryGene regulationSp1 promoterConsensus motifLocalization sequenceTATA motifStart siteTATA boxInitiator elementLocalization elementsWidespread roleA Comprehensive Model of the Spectrin Divalent Tetramer Binding Region Deduced Using Homology Modeling and Chemical Cross-linking of a Mini-spectrin [S] *
Li D, Harper SL, Tang HY, Maksimova Y, Gallagher PG, Speicher DW. A Comprehensive Model of the Spectrin Divalent Tetramer Binding Region Deduced Using Homology Modeling and Chemical Cross-linking of a Mini-spectrin [S] *. Journal Of Biological Chemistry 2010, 285: 29535-29545. PMID: 20610390, PMCID: PMC2937985, DOI: 10.1074/jbc.m110.145573.Peer-Reviewed Original ResearchConceptsHelix faceRed cell membrane stabilityHomology modelingNon-homologous tailsCell membrane stabilityC-terminal tailWild-type bindingMedium-resolution structureSubtle conformational changesTetramer complexSpectrin tetramer formationChemical Cross-LinkingMembrane skeletonRecombinant domainsTetramer formationFunctional 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
Structural and functional effects of hereditary hemolytic anemia-associated point mutations in the alpha spectrin tetramer site
Gaetani M, Mootien S, Harper S, Gallagher PG, Speicher DW. Structural and functional effects of hereditary hemolytic anemia-associated point mutations in the alpha spectrin tetramer site. Blood 2008, 111: 5712-5720. PMID: 18218854, PMCID: PMC2424163, DOI: 10.1182/blood-2007-11-122457.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnemia, Hemolytic, CongenitalBinding SitesCalorimetry, Differential ScanningCircular DichroismEntropyErythrocytesGene ExpressionGenotypeHumansMolecular Sequence DataPhenotypePoint MutationProtein BindingRecombinant ProteinsSpectrinSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationStructure-Activity Relationship
2007
An 11-amino acid β-hairpin loop in the cytoplasmic domain of band 3 is responsible for ankyrin binding in mouse erythrocytes
Stefanovic M, Markham NO, Parry EM, Garrett-Beal LJ, Cline AP, Gallagher PG, Low PS, Bodine DM. An 11-amino acid β-hairpin loop in the cytoplasmic domain of band 3 is responsible for ankyrin binding in mouse erythrocytes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 13972-13977. PMID: 17715300, PMCID: PMC1950715, DOI: 10.1073/pnas.0706266104.Peer-Reviewed Original ResearchConceptsCytoplasmic domainBeta-hairpin loopSpectrin-actinPlasma membraneBand 3Transmembrane protein band 3Β-hairpin loopProtein band 3Uncharacterized interactionMembrane proteinsProtein ankyrinCytoskeletal networkMembrane cytoskeletonCytoskeletal systemAnkyrinCurrent structural modelsErythrocyte membranesSLC4A1 geneLoop deletionComplete deficiencyDeletionMembraneMouse erythrocytesStructural supportDomain
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 expression
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-Binding ProteinsDNA, ComplementaryErythrocytesErythroid-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 geneMutation of a highly conserved isoleucine disrupts hydrophobic interactions in the αβ spectrin self-association binding site
Gallagher PG, Zhang Z, Morrow JS, Forget BG. Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the αβ spectrin self-association binding site. Laboratory Investigation 2004, 84: 229-234. PMID: 14661034, DOI: 10.1038/labinvest.3700029.Peer-Reviewed Original ResearchConceptsBinding sitesAlpha-spectrin mutationsEvolutionary conservationSpectrin functionSpectrin repeatsTriple helical modelAlpha-spectrinGenetic studiesHydrophobic isoleucineHydrophobic interactionsLow-expression alleleMolecular modelingExpression alleleSpectrinFunctional defectsTriple helixMutationsHelical modelIsoleucineErythrocyte membranesDrosophilaClinical phenotypeNeonatal hemolytic anemiaRepeatsHelix
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-Binding ProteinsDNA, ComplementaryErythroid 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