2017
Immature Lymphocytes Inhibit Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double-Strand Breaks
Fisher MR, Rivera-Reyes A, Bloch NB, Schatz DG, Bassing CH. Immature Lymphocytes Inhibit Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double-Strand Breaks. The Journal Of Immunology 2017, 198: 2943-2956. PMID: 28213501, PMCID: PMC5360515, DOI: 10.4049/jimmunol.1601639.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksDNA damage responseRAG1/RAG2Double-strand breaksRAG DNA double-strand breaksMultiple genomic locationsTranscription of genesNF-κB transcription factorsDSB responseGenomic integrityGenomic locationATM kinaseTranscriptional repressionRAG cleavageCellular functionsDamage responseLocus recombinationMammalian cellsRAG1 proteinTranscription factorsModulator proteinRAG expressionAtaxia telangiectasiaTranscriptional inhibitionDevelopmental stages
2015
Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia
Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon SM, Trageser D, Hasselfeld B, Henke N, Mooster J, Geng H, Schwarz K, Kogan SC, Casellas R, Schatz DG, Lieber MR, Greaves MF, Müschen M. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nature Immunology 2015, 16: 766-774. PMID: 25985233, PMCID: PMC4475638, DOI: 10.1038/ni.3160.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnimalsAntibody DiversityB-LymphocytesChildChild, PreschoolClonal EvolutionCytidine DeaminaseDNA-Binding ProteinsFemaleFlow CytometryHomeodomain ProteinsHumansImmunoblottingInfantMaleMice, Inbred NODMice, KnockoutMice, SCIDMice, TransgenicMicroscopy, FluorescencePrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidReverse Transcriptase Polymerase Chain ReactionTumor Cells, Cultured
2004
B cell–specific loss of histone 3 lysine 9 methylation in the VH locus depends on Pax5
Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K. B cell–specific loss of histone 3 lysine 9 methylation in the VH locus depends on Pax5. Nature Immunology 2004, 5: 853-861. PMID: 15258579, PMCID: PMC1635547, DOI: 10.1038/ni1099.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceB-LymphocytesCell LineageCells, CulturedDNA-Binding ProteinsFlow CytometryGene Rearrangement, B-LymphocyteHematopoietic Stem CellsHistonesImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionLysineMethylationMiceModels, ImmunologicalMolecular Sequence DataPAX5 Transcription FactorPrecipitin TestsReverse Transcriptase Polymerase Chain ReactionTranscription FactorsConceptsH3-K9 methylationDJH recombinationVH locusHistone 3 lysine 9 methylationLysine 9 methylationFunction of Pax5Non-B lineage cellsB cell-specific lossB cell commitmentHistone exchangeInactive chromatinLysine 9Histone H3Transcription factorsCell commitmentCell-specific lossInhibitory modificationMethylationLineage cellsLociPAX5B cellsHeavy chain rearrangementRecombinationChain rearrangementStaggered AID‐dependent DNA double strand breaks are the predominant DNA lesions targeted to Sµ in Ig class switch recombination
Rush JS, Fugmann SD, Schatz DG. Staggered AID‐dependent DNA double strand breaks are the predominant DNA lesions targeted to Sµ in Ig class switch recombination. International Immunology 2004, 16: 549-557. PMID: 15039385, DOI: 10.1093/intimm/dxh057.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBlotting, SouthernB-LymphocytesCell DivisionCytidine DeaminaseDeoxyribonucleases, Type II Site-SpecificDNADNA DamageDNA PrimersFlow CytometryGene ExpressionImmunoglobulin Class SwitchingImmunoglobulin DImmunoglobulin GImmunoglobulin Switch RegionInterleukin-4LipopolysaccharidesMiceMice, Inbred C57BLMice, KnockoutPlasmidsPolymerase Chain ReactionRecombination, GeneticConceptsClass switch recombinationDNA double-strand breaksPredominant DNA lesionsDouble-strand breaksActivation-induced cytidine deaminaseDNA lesionsSwitch recombinationAID-dependent DNA double-strand breaksStrand breaksIg class switch recombinationLigation-mediated PCRS mu regionCellular regulationKinetics of inductionMolecular detailsMurine B cellsDNA DSBsStaggered breaksCytidine deaminaseDSBsMu regionMinor speciesB cellsS muEffector propertiesPartial reconstitution of V(D)J rearrangement and lymphocyte development in RAG-deficient mice expressing inducible, tetracycline-regulated RAG transgenes
Shockett PE, Zhou S, Hong X, Schatz DG. Partial reconstitution of V(D)J rearrangement and lymphocyte development in RAG-deficient mice expressing inducible, tetracycline-regulated RAG transgenes. Molecular Immunology 2004, 40: 813-829. PMID: 14687938, DOI: 10.1016/j.molimm.2003.09.009.Peer-Reviewed Original ResearchConceptsPeripheral lymphoid organsIGK locusInducible gene expressionLymph nodesCell reconstitutionLymphoid organsTransgenic miceTRB locusTRD locusT-cell reconstitutionB-cell reconstitutionMammalian cellsRAG-deficient miceSignal endsTra locusRecombination signalsInducible activationGene expressionTCR beta chainFunctional expressionLymphocyte developmentLociRAG2 mRNALymphocyte reconstitutionTransgeneCloning of Apoptosis-Related Genes by Representational Difference Analysis of cDNA
Hubank M, Bryntesson F, Regan J, Schatz DG. Cloning of Apoptosis-Related Genes by Representational Difference Analysis of cDNA. Methods In Molecular Biology 2004, 282: 255-273. PMID: 15105570, DOI: 10.1385/1-59259-812-9:255.Peer-Reviewed Original ResearchConceptsRepresentational difference analysisApoptosis-related genesComplementary DNA representational difference analysisCDNA-RDAGene expressionDifferential gene expression analysisIdentification of genesKey target genesExpression levelsGene expression analysisLow-abundance transcriptsGene microarray analysisModel organismsTranscriptional differencesTarget genesExpression analysisDifferential displayMicroarray analysisGene microarrayCDNA fragmentsCDNA ampliconsGenesBase pairsSerial analysisPolymerase chain reaction amplification
1996
Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo.
Hoffman ES, Passoni L, Crompton T, Leu TM, Schatz DG, Koff A, Owen MJ, Hayday AC. Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo. Genes & Development 1996, 10: 948-962. PMID: 8608942, DOI: 10.1101/gad.10.8.948.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, T-LymphocyteCell CycleCell SeparationClone CellsCyclinsDNA-Binding ProteinsFemaleFlow CytometryFluorescent Antibody Technique, IndirectGene Expression Regulation, DevelopmentalGene Rearrangement, beta-Chain T-Cell Antigen ReceptorHomeodomain ProteinsHyaluronan ReceptorsMiceMice, Inbred C57BLProteinsReceptors, Antigen, T-Cell, alpha-betaReceptors, Interleukin-2Retinoblastoma ProteinRNA, MessengerThymus GlandT-LymphocytesConceptsTCRbeta chain genesBeta selectionT-cell receptor beta-chain locusChain geneTCRbeta chain gene rearrangementAlpha beta T cell developmentProductive gene rearrangementHyperphosphorylation of RbGene rearrangementsTCR gene rearrangementsTransition of thymocytesTCRbeta gene rearrangementT cell developmentRegulation of p27Coincident regulationBeta-chain locusPopulation of cellsTCR lociCell cycleCdc2 activityCDK2 activityTCRbeta selectionCyclin AThymocyte expansionCell phenotype
1995
Down-regulation of RAG1 and RAG2 gene expression in PreB cells after functional immunoglobulin heavy chain rearrangement
Grawunder U, Leu T, Schatz D, Werner A, Rolink A, Melchers F, Winkler T. Down-regulation of RAG1 and RAG2 gene expression in PreB cells after functional immunoglobulin heavy chain rearrangement. Immunity 1995, 3: 601-608. PMID: 7584150, DOI: 10.1016/1074-7613(95)90131-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceB-LymphocytesCell DifferentiationCell LineDNA-Binding ProteinsDown-RegulationFemaleFlow CytometryGene Rearrangement, B-LymphocyteHomeodomain ProteinsImmunoglobulin Heavy ChainsMiceMice, Inbred C57BLMice, Inbred DBAMice, Inbred StrainsMolecular Sequence DataPolymerase Chain ReactionProtein BiosynthesisProteinsProto-Oncogene Proteins c-kitReceptors, Antigen, B-CellRNA, MessengerConceptsRAG2 gene expressionPreB cellsGene expressionFunctional immunoglobulin genesPreB-II cellsPreB cell receptorB cell developmentCell cycle statusHeavy chain allelesRAG2 proteinsPostranscriptional levelImmature B cellsRAG genesGene productsTranscriptional levelProductive rearrangementsMouse bone marrowCell developmentDifferential surface expressionImmunoglobulin genesRAG1Cell surfaceRAG2 mRNAGenesCycle status
1991
Selective expression of RAG-2 in chicken B cells undergoing immunoglobulin gene conversion
Carlson L, Oettinger M, Schatz D, Masteller E, Hurley E, McCormack W, Baltimore D, Thompson C. Selective expression of RAG-2 in chicken B cells undergoing immunoglobulin gene conversion. Cell 1991, 64: 201-208. PMID: 1986866, DOI: 10.1016/0092-8674(91)90221-j.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBlotting, NorthernB-LymphocytesBursa of FabriciusCell LineChickensCloning, MolecularFlow CytometryGene ConversionGene ExpressionGene Expression RegulationGenes, ImmunoglobulinHumansMolecular Sequence DataNucleic Acid HybridizationRecombination, GeneticRNA, MessengerSpleenThymus GlandConceptsIg gene conversionGene conversionChicken B cellsRAG-2 mRNARAG-2Cis-acting DNA elementsChicken B cell lineRAG-1Mammalian B cellsIntrachromosomal gene conversionImmunoglobulin gene conversionRAG-2 expressionB cell developmentIg diversificationRAG-1 mRNADNA elementsCell developmentB cell linesBursa of FabriciusB cellsPhenotypic characteristicsSelective expressionCell linesBursal lymphocytesMRNA