2022
Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences.
Tarsalainen A, Maman Y, Meng FL, Kyläniemi MK, Soikkeli A, Budzyńska P, McDonald JJ, Šenigl F, Alt FW, Schatz DG, Alinikula J. Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences. The Journal Of Immunology 2022, 208: 143-154. PMID: 34862258, PMCID: PMC8702490, DOI: 10.4049/jimmunol.2100923.Peer-Reviewed Original ResearchConceptsPol IIMutating geneSomatic hypermutationTarget genesChicken DT40 B cellsRNA polymerase II stallingIg genesHistone variant H3.3Locus-specific targetingPol II occupancyAID-mediated mutationsDT40 B cellsRNA polymerase IILevels of H3K27acFull-length transcriptsVariant H3.3Antisense transcriptionTranscriptional outputPolymerase IIGenetic diversityMechanistic basisBurkitt's lymphoma cellsGeneration of AbsGenesDIVAC
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
2016
Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells
Williams AM, Maman Y, Alinikula J, Schatz DG. Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells. PLOS ONE 2016, 11: e0149146. PMID: 26900682, PMCID: PMC4762950, DOI: 10.1371/journal.pone.0149146.Peer-Reviewed Original ResearchConceptsDT40 cellsGene conversionTarget genesClass switch recombinationGene bodiesSomatic hypermutationB cell gene expression programChicken DT40 B cellsBCL6 functionCell gene expression programChicken DT40 cellsDT40 B cellsGene expression programsRNA polymerase IIDeficient DT40 cellsTranscription start siteExpression of AIDAbsence of Bcl6High-level expressionB cellsExpression programsPolymerase IIPol IIStart siteTranscriptional features
2014
Targeting Of Somatic Hypermutation By immunoglobulin Enhancer And Enhancer-Like Sequences
Buerstedde JM, Alinikula J, Arakawa H, McDonald JJ, Schatz DG. Targeting Of Somatic Hypermutation By immunoglobulin Enhancer And Enhancer-Like Sequences. PLOS Biology 2014, 12: e1001831. PMID: 24691034, PMCID: PMC3972084, DOI: 10.1371/journal.pbio.1001831.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesBinding SitesB-LymphocytesCell LineChickensCytidine DeaminaseE-Box ElementsEnhancer Elements, GeneticGene Knockout TechniquesGreen Fluorescent ProteinsHumansImmunoglobulin kappa-ChainsImmunoglobulin lambda-ChainsLymphocyte ActivationMEF2 Transcription FactorsMiceMutationNF-kappa BSequence AlignmentSomatic Hypermutation, ImmunoglobulinTranscription, GeneticUracil-DNA GlycosidaseConceptsSomatic hypermutationIg enhancersNovel regulatory functionStimulation of transcriptionEnhancer-like elementCytidine deaminase proteinEnhancer-like sequenceActivation-induced cytidine deaminase proteinGene specificityTranscriptional roleHeavy chain intron enhancerTranscription unitGenetic diversityEts familyE-boxChicken cellsRegulatory functionsIntron enhancerFull activationImmunoglobulin genesTarget sequenceImmunoglobulin enhancerPoint mutationsEnhancerTranscription
2012
Identification of Core DNA Elements That Target Somatic Hypermutation
Kohler KM, McDonald JJ, Duke JL, Arakawa H, Tan S, Kleinstein SH, Buerstedde JM, Schatz DG. Identification of Core DNA Elements That Target Somatic Hypermutation. The Journal Of Immunology 2012, 189: 5314-5326. PMID: 23087403, PMCID: PMC3664039, DOI: 10.4049/jimmunol.1202082.Peer-Reviewed Original ResearchMeSH Keywords3' Flanking RegionAnimalsB-LymphocytesCells, CulturedChickensChromatin ImmunoprecipitationCytidine DeaminaseDNAEnhancer Elements, GeneticGenes, ImmunoglobulinGenetic LociImmunoassayImmunoglobulin Variable RegionMutationPhosphorylationRNA Polymerase IISerineSomatic Hypermutation, ImmunoglobulinTranscription, GeneticConceptsActivation-induced deaminaseDNA elementsSomatic hypermutationChicken DT40 B cellsIg lociChromatin immunoprecipitation experimentsDT40 B cellsRNA polymerase IISystematic deletion analysisL chain lociNon-Ig genesCore DNA elementSerine 5Epigenetic marksPolymerase IITranscriptional elongationMutational machineryDeletion analysisReporter cassetteImmunoprecipitation experimentsDeoxycytosine residuesIg genesDNA damageChain locusLoci
2011
A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation
Seitan VC, Hao B, Tachibana-Konwalski K, Lavagnolli T, Mira-Bontenbal H, Brown KE, Teng G, Carroll T, Terry A, Horan K, Marks H, Adams DJ, Schatz DG, Aragon L, Fisher AG, Krangel MS, Nasmyth K, Merkenschlager M. A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation. Nature 2011, 476: 467-471. PMID: 21832993, PMCID: PMC3179485, DOI: 10.1038/nature10312.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell DifferentiationChromosomal Proteins, Non-HistoneDNA-Binding ProteinsGene Expression RegulationGene Rearrangement, T-LymphocyteGenes, RAG-1MiceNuclear ProteinsPhosphoproteinsReceptors, Antigen, T-Cell, alpha-betaRecombinasesThymus GlandTranscription, Genetic
2010
Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination
Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, Schatz DG. Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. Journal Of Experimental Medicine 2010, 207: 2809-2816. PMID: 21115692, PMCID: PMC3005232, DOI: 10.1084/jem.20101136.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBinding, CompetitiveChromatin ImmunoprecipitationDNAEnhancer Elements, GeneticFemaleGene RearrangementGenes, ImmunoglobulinGenotypeHistonesHMGB1 ProteinHomeodomain ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticProtein BindingReceptors, Antigen, T-Cell, alpha-betaRecombination, GeneticTranscription, GeneticVDJ Recombinases
2007
Activation-induced Cytidine Deaminase-mediated Sequence Diversification Is Transiently Targeted to Newly Integrated DNA Substrates*
Yang SY, Fugmann SD, Gramlich HS, Schatz DG. Activation-induced Cytidine Deaminase-mediated Sequence Diversification Is Transiently Targeted to Newly Integrated DNA Substrates*. Journal Of Biological Chemistry 2007, 282: 25308-25313. PMID: 17613522, DOI: 10.1074/jbc.m704231200.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseChicken B cell line DT40B cell line DT40Cytidine deaminaseNon-Ig lociNon-Ig genesSequence diversificationDNA substratesTranscription cassetteMutation targetsCassetteMolecular characteristicsMolecular featuresDeaminaseDT40TranscriptionGenesLociDNADiversificationMutabilityTargetingIgTarget
2006
Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences
Yang SY, Fugmann SD, Schatz DG. Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences. Journal Of Experimental Medicine 2006, 203: 2919-2928. PMID: 17178919, PMCID: PMC2118177, DOI: 10.1084/jem.20061835.Peer-Reviewed Original ResearchActinsAnimalsBacteriophage T7B-LymphocytesCell Line, TumorCytidine DeaminaseEnhancer Elements, GeneticGene ConversionGene DeletionGene ExpressionGenes, Immunoglobulin Light ChainImmunoglobulin Heavy ChainsImmunoglobulin MMutationPeptide Elongation Factor 1Promoter Regions, GeneticReceptors, Antigen, B-CellSomatic Hypermutation, ImmunoglobulinTranscription, GeneticTransfection
2005
B cells and osteoblast and osteoclast development
Horowitz MC, Bothwell AL, Hesslein DG, Pflugh DL, Schatz DG. B cells and osteoblast and osteoclast development. Immunological Reviews 2005, 208: 141-153. PMID: 16313346, DOI: 10.1111/j.0105-2896.2005.00328.x.Peer-Reviewed Original ResearchAnimalsB-LymphocytesCarrier ProteinsCell DifferentiationDNA-Binding ProteinsGlycoproteinsHumansInterleukin-7LymphopoiesisMembrane GlycoproteinsOsteoblastsOsteoclastsOsteogenesisOsteoprotegerinPAX5 Transcription FactorRANK LigandReceptor Activator of Nuclear Factor-kappa BReceptors, Cytoplasmic and NuclearReceptors, Tumor Necrosis FactorTrans-ActivatorsTranscription, Genetic
2003
Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments
Hesslein DG, Pflugh DL, Chowdhury D, Bothwell AL, Sen R, Schatz DG. Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments. Genes & Development 2003, 17: 37-42. PMID: 12514097, PMCID: PMC195966, DOI: 10.1101/gad.1031403.Peer-Reviewed Original ResearchAcetylationAllelesAnimalsB-LymphocytesChromatinDNA NucleotidyltransferasesDNA-Binding ProteinsGene Rearrangement, B-Lymphocyte, Heavy ChainGenes, ImmunoglobulinGenes, RAG-1HistonesHomeodomain ProteinsImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Inbred C57BLMice, KnockoutPAX5 Transcription FactorTranscription FactorsTranscription, GeneticVDJ Recombinases
2000
Cell-cycle-regulated DNA double-strand breaks in somatic hypermutation of immunoglobulin genes
Papavasiliou F, Schatz D. Cell-cycle-regulated DNA double-strand breaks in somatic hypermutation of immunoglobulin genes. Nature 2000, 408: 216-221. PMID: 11089977, DOI: 10.1038/35041599.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksDouble-strand breaksSomatic hypermutationRepair of DSBsVariable region promotersImmunoglobulin variable region genesDNA replicationHomologous recombinationHeterologous promoterSpecific residuesVariable genesNearby mutationsRegion promoterVariable region genesImmunoglobulin genesHeterologous sequencesChromosomal translocationsPoint mutationsGenesRegion genesMutationsHypermutationTranscriptionPromoterB-cell tumors
1991
The recombination activating gene-1 (RAG-1) transcript is present in the murine central nervous system
Chun J, Schatz D, Oettinger M, Jaenisch R, Baltimore D. The recombination activating gene-1 (RAG-1) transcript is present in the murine central nervous system. Cell 1991, 64: 189-200. PMID: 1986864, DOI: 10.1016/0092-8674(91)90220-s.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsBase SequenceBrainCell DivisionCell LineChromosome MappingCytarabineGenesMiceMice, Inbred BALB CMolecular Sequence DataNeuronsNucleic Acid HybridizationOligonucleotide ProbesOrgan SpecificityPolymerase Chain ReactionRecombination, GeneticRNA ProbesTeratomaTranscription, GeneticTretinoinConceptsCentral nervous systemRAG-1 transcriptsMurine central nervous systemNervous systemHigh neuronal cell densityRAG-2 transcriptsSite-specific recombination machineryNeuronal cell densityNorthern blot analysisRecombination machineryGenome sitesPolymerase chain reactionRAG-2Postnatal brainPostnatal neuronsDetrimental alterationsRAG-1TranscriptsSitu hybridizationBlot analysisChain reactionNeuronsCell densityRecombination