2019
MKL1-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
2012
MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation
Smith EC, Thon JN, Devine MT, Lin S, Schulz VP, Guo Y, Massaro SA, Halene S, Gallagher P, Italiano JE, Krause DS. MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation. Blood 2012, 120: 2317-2329. PMID: 22806889, PMCID: PMC3447785, DOI: 10.1182/blood-2012-04-420828.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateAnimalsBleeding TimeBlood PlateletsBone Marrow CellsCells, CulturedCrosses, GeneticCytoplasmCytoskeletonGene Expression ProfilingHematopoiesisMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisPlatelet ActivationThrombocytopeniaTrans-ActivatorsTranscription FactorsConceptsMegakaryocyte maturationPlatelet formationSerum response factorSerum response factor expressionMembrane organizationGene expressionMKL1MKL2Response factorDKO miceKO backgroundMegakaryocyte compartmentMegakaryocytesCritical roleMegakaryocyte ploidyExpressionMaturationKnockout miceFactor expressionCrucial roleHomologuesGenesMiceProlonged bleeding timeRoleAltered subcellular localization of transcription factor TEAD4 regulates first mammalian cell lineage commitment
Home P, Saha B, Ray S, Dutta D, Gunewardena S, Yoo B, Pal A, Vivian JL, Larson M, Petroff M, Gallagher PG, Schulz VP, White KL, Golos TG, Behr B, Paul S. Altered subcellular localization of transcription factor TEAD4 regulates first mammalian cell lineage commitment. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 7362-7367. PMID: 22529382, PMCID: PMC3358889, DOI: 10.1073/pnas.1201595109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlastocystBlastocyst Inner Cell MassBlastomeresBlotting, WesternCattleCDX2 Transcription FactorCell LineageCell NucleusCells, CulturedDNA-Binding ProteinsEmbryonic Stem CellsGATA3 Transcription FactorGene Expression Regulation, DevelopmentalGreen Fluorescent ProteinsHEK293 CellsHomeodomain ProteinsHumansMacaca mulattaMiceMice, TransgenicMuscle ProteinsRatsReverse Transcriptase Polymerase Chain ReactionRNA InterferenceTEA Domain Transcription FactorsTranscription FactorsConceptsInner cell massTranscriptional programsICM lineagesSubcellular localizationNuclear localizationInner blastomeresCell fate specificationSpecific transcriptional programsCell lineage commitmentAltered subcellular localizationTranscription factor TEAD4Preimplantation mouse embryosFate specificationLineage commitmentTarget genesMouse embryosCell lineagesTEAD4LineagesBlastomeresBlastocyst formationCell massDifferential functionGenesLocalization
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
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 erythrocytesExpressionSpectrinAnkyrin‐linked hereditary spherocytosis in an African–American kindred
Sangerman J, Maksimova Y, Edelman EJ, Morrow JS, Forget BG, Gallagher PG. Ankyrin‐linked hereditary spherocytosis in an African–American kindred. American Journal Of Hematology 2008, 83: 789-794. PMID: 18704959, PMCID: PMC11304496, DOI: 10.1002/ajh.21254.Peer-Reviewed Original ResearchConceptsInitiator methionineNull allelesErythrocyte membrane protein genesMembrane protein geneRabbit reticulocyte lysateTissue-specific promotersErythrocyte membrane skeletonExon 1 sequencesIsoform diversityAlternative splicingTranslation initiationProtein geneAnkyrin geneMembrane skeletonAlternate polyadenylationPlasma membraneReticulocyte lysateMethionine mutationCOOH terminusErythroid cellsDownstream codonsGenomic DNANumerous isoformsAnkyrinGenes
2007
Novel 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
2005
Molecular mechanisms in the inherited red cell membrane disorders
Liem R, Gallagher P. Molecular mechanisms in the inherited red cell membrane disorders. Drug Discovery Today Disease Mechanisms 2005, 2: 539-545. DOI: 10.1016/j.ddmec.2005.11.004.Peer-Reviewed Original ResearchRed cell membrane disordersSingle molecular defectEpigenetic controlMRNA processingProtein functionGene expressionMolecular mechanismsMolecular defectsErythrocyte membrane structureRed cell membrane abnormalitiesMembrane structureMolecular medicineMutationsMembrane disordersDiverse groupCurrent knowledgeGenesRegion mutationsMolecular heterogeneityPromoter mutationsCell membrane abnormalitiesErythrocyte membranesInherited disorderMembrane abnormalitiesProteinMultiple isoforms of the KC1 cotransporter are expressed in sickle and normal erythroid cells
Crable SC, Hammond SM, Papes R, Rettig RK, Zhou GP, Gallagher PG, Joiner CH, Anderson KP. Multiple isoforms of the KC1 cotransporter are expressed in sickle and normal erythroid cells. Experimental Hematology 2005, 33: 624-631. PMID: 15911086, DOI: 10.1016/j.exphem.2005.02.006.Peer-Reviewed Original ResearchConceptsErythroid cellsKCC isoformsMultiple isoformsSplicing variantsStructure/function studiesKCl cotransporterWild-type cellsHuman erythroid cellsDifferentiated erythroid precursorsCl-dependent K fluxTransient transfection experimentsNormal erythroid cellsIsoform expression patternCotransporter activityRed cellsKCC genesExpression patternsReticulocyte maturationHuman red cellsKCC1 geneTransfection experimentsReverse transcriptase-PCRSplice variantsRelative abundanceGenes
2001
Development of a Stable Retrovirus Vector Capable of Long‐Term Expression of γ‐Globin mRNA in Mouse Erythrocytes
SABATINO D, SEIDEL N, CLINE A, ANDERSON S, GALLAGHER P, BODINE D. Development of a Stable Retrovirus Vector Capable of Long‐Term Expression of γ‐Globin mRNA in Mouse Erythrocytes. Annals Of The New York Academy Of Sciences 2001, 938: 246-261. PMID: 11458514, DOI: 10.1111/j.1749-6632.2001.tb03595.x.Peer-Reviewed Original ResearchConceptsGamma-globin geneLocus control regionGamma-globin mRNARetrovirus vectorHematopoietic stem cellsGene promoterHuman gamma-globin geneMouse alpha-globin mRNAGlobin gene promoterAlpha-globin mRNAStem cellsMature red blood cellsNumber-dependent expressionMouse progenitor cellsΓ-globin mRNAGlobin genesControl regionLevel of expressionStable gene transferGenesGene transferPromoterProgenitor cellsGene therapyMRNA
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 disordersGenesPromoter
1999
Stomatocytosis is absent in "stomatin"-deficient murine red blood cells.
Zhu Y, Paszty C, Turetsky T, Tsai S, Kuypers F, Lee G, Cooper P, Gallagher P, Stevens M, Rubin E, Mohandas N, Mentzer W. Stomatocytosis is absent in "stomatin"-deficient murine red blood cells. Blood 1999, 93: 2404-10. PMID: 10090952, DOI: 10.1182/blood.v93.7.2404.407k13_2404_2410.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Hemolytic, CongenitalAnimalsBlood ProteinsCarrier ProteinsCationsErythrocyte DeformabilityErythrocyte IndicesErythrocyte MembraneErythrocytes, AbnormalFemaleGenotypeHumansIon TransportMaleMembrane FluidityMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutPhenotypePhosphatidylserinesPhospholipid Transfer ProteinsPotassiumSodiumStomatocytosis Is Absent in “Stomatin”-Deficient Murine Red Blood Cells
Zhu Y, Paszty C, Turetsky T, Tsai S, Kuypers F, Lee G, Cooper P, Gallagher P, Stevens M, Rubin E, Mohandas N, Mentzer W. Stomatocytosis Is Absent in “Stomatin”-Deficient Murine Red Blood Cells. Blood 1999, 93: 2404-2410. DOI: 10.1182/blood.v93.7.2404.Peer-Reviewed Original Research
1997
Spectrin St Claude, a Splicing Mutation of the Human α-Spectrin Gene Associated With Severe Poikilocytic Anemia
Fournier C, Nicolas G, Gallagher P, Dhermy D, Grandchamp B, Lecomte M. Spectrin St Claude, a Splicing Mutation of the Human α-Spectrin Gene Associated With Severe Poikilocytic Anemia. Blood 1997, 89: 4584-4590. PMID: 9192783, DOI: 10.1182/blood.v89.12.4584.Peer-Reviewed Original ResearchConceptsAlpha-spectrin chainAcceptor splice siteSplice siteSplicing mutationAlpha-spectrin geneΑ-spectrin geneExon 20New acceptor splice siteMolecular basisTermination codonNovel mRNAInsertion upstreamTract mutationsTryptic digestionMutationsG mutationGenesMRNAHeterozygous parentsErythrocyte membranesMembraneFrame skippingCodonSitesVariants
1996
Epidemiological studies of spectrin mutations related to hereditary elliptocytosis and spectrin polymorphisms in Benin
Glele‐Kakai C, Garbarz M, Lecomte M, Leborgne S, Galand C, Bournier O, Devaux I, Gautero H, Zohoun I, Gallagher P, Forget B, Dhermy D. Epidemiological studies of spectrin mutations related to hereditary elliptocytosis and spectrin polymorphisms in Benin. British Journal Of Haematology 1996, 95: 57-66. PMID: 8857939, DOI: 10.1046/j.1365-2141.1996.d01-1869.x.Peer-Reviewed Original ResearchConceptsHereditary elliptocytosisGenetic backgroundAlpha-spectrin geneSeparate genetic backgroundsNumber of polymorphismsErythrocyte alpha-spectrinGenetic basisProtein polymorphismsAfrican populationsAlpha-spectrinSpectrin mutationsMolecular defectsMutationsNovel mutationsPolymorphismEpidemiological studiesHE individualsElliptocytosisTwo-thirdsGenesSpectrinPopulationHigh frequencyMolecular basis and haplotyping of the alphaII domain polymorphisms of spectrin: application to the study of hereditary elliptocytosis and pyropoikilocytosis.
Gallagher PG, Kotula L, Wang Y, Marchesi SL, Curtis PJ, Speicher DW, Forget BG. Molecular basis and haplotyping of the alphaII domain polymorphisms of spectrin: application to the study of hereditary elliptocytosis and pyropoikilocytosis. American Journal Of Human Genetics 1996, 59: 351-9. PMID: 8755921, PMCID: PMC1914747.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnemia, Hemolytic, CongenitalAsianAsian PeopleBase SequenceBiological EvolutionBlack PeopleElliptocytosis, HereditaryErythrocytes, AbnormalHaplotypesHumansModels, GeneticMolecular Sequence DataMutagenesis, InsertionalPolymorphism, GeneticPrevalenceRepetitive Sequences, Nucleic AcidSpectrinUnited StatesWhite PeopleConceptsAlpha-spectrin geneAmino acid sequenceAcid sequenceHereditary elliptocytosisAlpha-spectrin chainHereditary pyropoikilocytosisPrincipal structural proteinErythrocyte membrane skeletonSingle nucleotide substitutionEvolutionary originLimited tryptic digestionMembrane skeletonMolecular basisGenomic DNANucleotide substitutionsStructural proteinsAlpha-spectrinDifferent haplotypesFounder effectGenesLinkage disequilibriumOnly haplotypeSpectrin proteinsCommon haplotypeTryptic digestionGenomic Organization and 5′-Flanking DNA Sequence of the Murine Stomatin Gene (Epb72)
Gallagher P, Turetsky T, Mentzer W. Genomic Organization and 5′-Flanking DNA Sequence of the Murine Stomatin Gene (Epb72). Genomics 1996, 34: 410-412. PMID: 8786142, DOI: 10.1006/geno.1996.0304.Peer-Reviewed Original ResearchConceptsStomatin geneDNA sequencesPotential DNA-binding proteinsIntegral membrane proteinsDNA-binding proteinsGenomic DNA sequencesHousekeeping gene promoterGenomic organizationExon structureGenomic structureChromosomal genesMembrane proteinsGene promoterConsensus sequenceGenomic DNAProtein structureGenesHereditary stomatocytosisSequenceProteinErythrocyte membranesStomatinCloningExonsPromoter
1995
Structure, Organization, and Expression of the Human Band 7.2b Gene, a Candidate Gene for Hereditary Hydrocytosis (∗)
Gallagher P, Forget B. Structure, Organization, and Expression of the Human Band 7.2b Gene, a Candidate Gene for Hereditary Hydrocytosis (∗). Journal Of Biological Chemistry 1995, 270: 26358-26363. PMID: 7592848, DOI: 10.1074/jbc.270.44.26358.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnemia, HemolyticAnimalsBase SequenceBlood ProteinsBlotting, NorthernCell LineConsensus SequenceDNA PrimersDNA, ComplementaryExonsGene ExpressionGenetic VariationHominidaeHumansIntronsLeukemia, Erythroblastic, AcuteMembrane ProteinsMiceMolecular Sequence DataPolymerase Chain ReactionPolymorphism, GeneticPromoter Regions, GeneticRecombinant Fusion ProteinsRegulatory Sequences, Nucleic AcidRestriction MappingRNA, MessengerTransfectionTumor Cells, CulturedConceptsSingle transcription initiation siteSimple sequence repeat polymorphismKilobases of DNATranscription initiation siteAlternative polyadenylation signalsFurther genetic studiesHigh-level expressionNorthern blot analysisPattern of expressionWide tissue distributionGenomic structureRich promoterNonerythroid cellsChromosomal genesPolyadenylation signalMembrane skeletonGene cDNAGene promoterReporter geneCandidate genesRecognition sequenceGenetic studiesInitiation siteGenesBase pairscDNA Structure, Tissue-Specific Expression, and Chromosomal Localization of the Murine Band 7.2b Gene
Gallagher P, Romana M, Lieman J, Ward D. cDNA Structure, Tissue-Specific Expression, and Chromosomal Localization of the Murine Band 7.2b Gene. Blood 1995, 86: 359-365. PMID: 7540886, DOI: 10.1182/blood.v86.1.359.bloodjournal861359.Peer-Reviewed Original ResearchConceptsTissue-specific expressionSingle membrane-spanning domainMembrane-spanning domainsBp of cDNAOpen reading frameChromosomal localizationSignificant homologyReading frameCDNA structureHuman homologueAlpha-helixProtein structureBeta sheetAmino acidsErythrocyte membranesGenesProximal regionDatabase searchingProteinSitu hybridizationCDNADistal regionWider patternsSkeletal muscleExpressionRecurrent fatal hydrops fetalis associated with a nucleotide substitution in the erythrocyte beta-spectrin gene.
Gallagher PG, Weed SA, Tse WT, Benoit L, Morrow JS, Marchesi SL, Mohandas N, Forget BG. Recurrent fatal hydrops fetalis associated with a nucleotide substitution in the erythrocyte beta-spectrin gene. Journal Of Clinical Investigation 1995, 95: 1174-1182. PMID: 7883966, PMCID: PMC441455, DOI: 10.1172/jci117766.Peer-Reviewed Original ResearchConceptsBeta-spectrin geneErythrocyte membrane mechanical stabilityPrincipal structural proteinMembrane mechanical stabilitySpectrin functionBeta spectrinErythrocyte membranesNucleotide substitutionsStudy of erythrocytesStructural proteinsAlpha-spectrinGenetic studiesMolecular defectsPoint mutationsSpectrinHydrops fetalisRecombinant peptideMutationsGenesSevere Coomb's negative hemolytic anemiaThird-trimester fetal loss