2019
Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting
Dinesh RK, Barnhill B, Ilanges A, Wu L, Michelson DA, Senigl F, Alinikula J, Shabanowitz J, Hunt DF, Schatz DG. Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting. European Journal Of Immunology 2019, 50: 380-395. PMID: 31821534, PMCID: PMC7202714, DOI: 10.1002/eji.201948357.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseGene conversionSomatic hypermutationIg genesTranscription factor family membersTrans-acting factorsFactor family membersClass switch recombinationEnhancer-like sequenceRamos B cell lineIgH intronic enhancerSecondary diversificationTranscription factorsE-boxFactor bindingChIP assaysIntronic enhancerReporter assaysB cell linesSpecific DNASwitch recombinationSHM targetingIg enhancersCytidine deaminaseNovel insights
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
Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein
Buerstedde JM, Lowndes N, Schatz DG. Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein. ELife 2014, 3: e03110. PMID: 25006166, PMCID: PMC4080448, DOI: 10.7554/elife.03110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceB-LymphocytesCell LineChickensCrossing Over, GeneticCytidine DeaminaseGene ConversionGenes, ReporterGreen Fluorescent ProteinsHomologous RecombinationHumansImmunoglobulin Switch RegionLuminescent ProteinsMiceModels, GeneticMolecular Sequence DataNucleic Acid HeteroduplexesRecombinational DNA RepairRepetitive Sequences, Nucleic AcidSequence DeletionSequence Homology, Nucleic AcidSomatic Hypermutation, ImmunoglobulinConceptsHomologous recombinationCytidine deaminase proteinSequence repeatsCytidine deaminationDNA end resectionHundreds of basesAnalysis of recombinantsVertebrate cellsGene conversionRepeat recombinationEnd resectionHolliday junctionsHomologous sequencesSequence homologyReporter transgeneStrand invasionIntergenic deletionRecombinogenic activityImmunoglobulin lociRepeatsSomatic hypermutationHeteroduplex formationRecombinationProteinDeamination
2007
Role of Activation-Induced Deaminase Protein Kinase A Phosphorylation Sites in Ig Gene Conversion and Somatic Hypermutation
Chatterji M, Unniraman S, McBride KM, Schatz DG. Role of Activation-Induced Deaminase Protein Kinase A Phosphorylation Sites in Ig Gene Conversion and Somatic Hypermutation. The Journal Of Immunology 2007, 179: 5274-5280. PMID: 17911613, DOI: 10.4049/jimmunol.179.8.5274.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsAvian ProteinsCell LineChickensCyclic AMP-Dependent Protein KinasesCytidine DeaminaseEnzyme ActivationGene ConversionGenes, ImmunoglobulinHumansMiceMolecular Sequence DataPhosphorylationSerineSomatic Hypermutation, ImmunoglobulinZebrafish ProteinsConceptsReplication protein AActivation-induced deaminaseProtein kinase AClass switch recombinationGene conversionDT40 cellsPhosphorylation sitesSomatic hypermutationProtein kinase A (PKA) phosphorylation siteChicken DT40 cellsIg gene conversionEfficient gene conversionConsensus target siteIg gene diversificationGene diversificationSerine 38Cytosine residuesKinase ASwitch recombinationIg genesResidue interferesFish proteinTarget siteProtein AS38Targeting of AID‐Mediated Sequence Diversification by cis‐Acting Determinants
Yang SY, Schatz DG. Targeting of AID‐Mediated Sequence Diversification by cis‐Acting Determinants. Advances In Immunology 2007, 94: 109-125. PMID: 17560273, DOI: 10.1016/s0065-2776(06)94004-8.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseSequence diversificationFeatures of chromatinTranscriptional control elementsCis-acting determinantsClass switch recombinationGene conversionDiversification processMolecular mechanismsIg lociSwitch recombinationIg genesAntibody diversityImmunoglobulin genesCytidine deaminaseSomatic hypermutationControl elementsTranscriptionGenesDiversificationRecombinationChromatinLociDiversityPermissive
2004
Non‐redundancy of cytidine deaminases in class switch recombination
Fugmann SD, Rush JS, Schatz DG. Non‐redundancy of cytidine deaminases in class switch recombination. European Journal Of Immunology 2004, 34: 844-849. PMID: 14991614, DOI: 10.1002/eji.200324418.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseClass switch recombinationAPOBEC-1Human activation-induced cytidine deaminaseSwitch recombinationCognate substratesCatalytic mutantGene conversionClose homologueProkaryotic cellsInactive mutantMurine B cellsDistinct mRNAsCytidine deaminase activityCytidine deaminasesImmunoglobulin genesDiversification mechanismsCytidine deaminaseSomatic hypermutationUnknown mechanismDeaminase activityMutantsPrecise roleActivated B cellsB cells
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