Featured Publications
HMCES protects immunoglobulin genes specifically from deletions during somatic hypermutation
Wu L, Shukla V, Yadavalli AD, Dinesh RK, Xu D, Rao A, Schatz DG. HMCES protects immunoglobulin genes specifically from deletions during somatic hypermutation. Genes & Development 2022, 36: 433-450. PMID: 35450882, PMCID: PMC9067407, DOI: 10.1101/gad.349438.122.Peer-Reviewed Original ResearchAnimalsCytidine DeaminaseDNADNA-Binding ProteinsGenes, ImmunoglobulinImmunoglobulin Class SwitchingMiceSomatic Hypermutation, ImmunoglobulinUracil
2020
Making ends meet in class switch recombination
Wu L, Schatz DG. Making ends meet in class switch recombination. Cell Research 2020, 30: 711-712. PMID: 32451457, PMCID: PMC7609326, DOI: 10.1038/s41422-020-0342-5.Peer-Reviewed Original Research
2019
TET enzymes augment activation-induced deaminase (AID) expression via 5-hydroxymethylcytosine modifications at the Aicda superenhancer
Lio CJ, Shukla V, Samaniego-Castruita D, González-Avalos E, Chakraborty A, Yue X, Schatz DG, Ay F, Rao A. TET enzymes augment activation-induced deaminase (AID) expression via 5-hydroxymethylcytosine modifications at the Aicda superenhancer. Science Immunology 2019, 4 PMID: 31028100, PMCID: PMC6599614, DOI: 10.1126/sciimmunol.aau7523.Peer-Reviewed Original ResearchMeSH Keywords5-MethylcytosineAnimalsBasic-Leucine Zipper Transcription FactorsB-LymphocytesCell DifferentiationCells, CulturedCytidine DeaminaseDioxygenasesDNA DemethylationDNA-Binding ProteinsGene Expression RegulationGenetic LociImmunoglobulin Class SwitchingLymphocyte ActivationMiceMice, TransgenicPrimary Cell CultureProto-Oncogene ProteinsResponse ElementsConceptsClass switch recombinationTranscription factorsChromatin accessibilityDNA demethylationBasic region-leucine zipper (bZIP) transcription factorsBZIP transcription factorsZipper transcription factorKey transcription factorEpigenetic marksTET enzymesEnhancer dynamicsGenomic regionsDeficient B cellsMurine B cellsEnhancer activityEnzyme essentialEnhancer elementsSwitch recombinationActivation-induced deaminase (AID) expressionAID expressionB cellsSuperenhancersTetDemethylationExpression
2010
Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions
Maul RW, Saribasak H, Martomo SA, McClure RL, Yang W, Vaisman A, Gramlich HS, Schatz DG, Woodgate R, Wilson DM, Gearhart PJ. Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nature Immunology 2010, 12: 70-76. PMID: 21151102, PMCID: PMC3653439, DOI: 10.1038/ni.1970.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigenic VariationB-LymphocytesCells, CulturedCytidine DeaminaseDNA-(Apurinic or Apyrimidinic Site) LyaseImmunoglobulin Class SwitchingImmunoglobulin Variable RegionInterleukin-4LipopolysaccharidesLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutModels, ChemicalSpleenUracilUracil-DNA Glycosidase
2007
Targeting 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 ResearchMeSH KeywordsAnimalsAntibody DiversityCytidine DeaminaseHumansImmunoglobulin Class SwitchingSomatic Hypermutation, ImmunoglobulinConceptsActivation-induced cytidine deaminaseSequence diversificationFeatures of chromatinTranscriptional control elementsCis-acting determinantsClass switch recombinationGene conversionDiversification processMolecular mechanismsIg lociSwitch recombinationIg genesAntibody diversityImmunoglobulin genesCytidine deaminaseSomatic hypermutationControl elementsTranscriptionGenesDiversificationRecombinationChromatinLociDiversityPermissive
2005
Expression of activation-induced cytidine deaminase is regulated by cell division, providing a mechanistic basis for division-linked class switch recombination
Rush JS, Liu M, Odegard VH, Unniraman S, Schatz DG. Expression of activation-induced cytidine deaminase is regulated by cell division, providing a mechanistic basis for division-linked class switch recombination. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 13242-13247. PMID: 16141332, PMCID: PMC1201576, DOI: 10.1073/pnas.0502779102.Peer-Reviewed Original ResearchConceptsClass switch recombinationCell divisionAID expressionSwitch recombinationFrequency of CSRSingle cell divisionSubsequent cell divisionSuccessive cell divisionsActivation-induced cytidine deaminaseConstitutive AID expressionIg heavy chain constant regionsEffector function propertiesHeavy chain constant regionActivation-induced cytidine deaminase mRNAMolecular explanationMechanistic basisDifferent molecular featuresSuccessive divisionsChain constant regionCytidine deaminaseB cell activationCytokine exposureExpressionConstant regionCell activationHistone Modifications Associated with Somatic Hypermutation
Odegard VH, Kim ST, Anderson SM, Shlomchik MJ, Schatz DG. Histone Modifications Associated with Somatic Hypermutation. Immunity 2005, 23: 101-110. PMID: 16039583, DOI: 10.1016/j.immuni.2005.05.007.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsB-LymphocytesChromatinChromatin ImmunoprecipitationCpG IslandsDNA DamageDNA MethylationHistonesImmunoglobulin Class SwitchingImmunoglobulin lambda-ChainsImmunoglobulin Light ChainsMethylationMiceMice, TransgenicPhosphorylationProtein Serine-Threonine KinasesSomatic Hypermutation, ImmunoglobulinConceptsClass switch recombinationSomatic hypermutationDistinct DNA damage responsesPhosphorylation of H2BHistone modification patternsDNA damage responseChromatin modificationsHistone modificationsKinase Mst1Histone H2BDamage responseHistone acetylationAcetylated H3Modification patternsPhosphorylated formIg lociSwitch recombinationImmunoglobulin lociH2BGammaH2AXLociHypermutationRecombinationHistonesH2AX
2004
Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc
Unniraman S, Zhou S, Schatz DG. Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc. Nature Immunology 2004, 5: 1117-1123. PMID: 15489857, DOI: 10.1038/ni1127.Peer-Reviewed Original ResearchUNGstoppable Switching
Unniraman S, Fugmann SD, Schatz DG. UNGstoppable Switching. Science 2004, 305: 1113-1114. PMID: 15326342, DOI: 10.1126/science.1102692.Peer-Reviewed Original ResearchStaggered 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 propertiesNon‐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 ResearchMeSH KeywordsAnimalsAPOBEC-1 DeaminaseB-LymphocytesCells, CulturedCytidine DeaminaseHumansImmunoglobulin Class SwitchingImmunoglobulin Switch RegionKineticsMiceMutationRatsConceptsActivation-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
2003
RNA AIDs DNA
Fugmann SD, Schatz DG. RNA AIDs DNA. Nature Immunology 2003, 4: 429-430. PMID: 12719733, DOI: 10.1038/ni0503-429.Peer-Reviewed Original ResearchMeSH KeywordsCytidine DeaminaseDNAHumansImmunoglobulin Class SwitchingModels, ImmunologicalRecombination, GeneticRNASomatic Hypermutation, Immunoglobulin
2002
Somatic Hypermutation of Immunoglobulin Genes Merging Mechanisms for Genetic Diversity
Papavasiliou FN, Schatz DG. Somatic Hypermutation of Immunoglobulin Genes Merging Mechanisms for Genetic Diversity. Cell 2002, 109: s35-s44. PMID: 11983151, DOI: 10.1016/s0092-8674(02)00706-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody DiversityCytidine DeaminaseDNA RepairGenes, ImmunoglobulinHumansImmunoglobulin Class SwitchingLymphomaRecombination, GeneticSomatic Hypermutation, ImmunoglobulinConceptsActivation-induced cytidine deaminaseSomatic hypermutationRNA editing enzymeDNA strand lesionsGenetic diversityEditing enzymeMolecular mechanismsRepair moleculesStrand lesionsCytidine deaminaseHypermutation processHypermutationRecent studiesModification reactionsEffective immune responseRecent advancesHigh-affinity antibodiesImmune responseDiversityEnzymePathwayMechanismDeaminaseDiscoveryOne AID to Unite Them All
Fugmann SD, Schatz DG. One AID to Unite Them All. Science 2002, 295: 1244-1245. PMID: 11847327, DOI: 10.1126/science.1070023.Peer-Reviewed Original Research
1996
Neoteny in Lymphocytes: Rag1 and Rag2 Expression in Germinal Center B Cells
Han S, Zheng B, Schatz D, Spanopoulou E, Kelsoe G. Neoteny in Lymphocytes: Rag1 and Rag2 Expression in Germinal Center B Cells. Science 1996, 274: 2094-2097. PMID: 8953043, DOI: 10.1126/science.274.5295.2094.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesDNA NucleotidyltransferasesDNA-Binding ProteinsFemaleGene ExpressionGene RearrangementGenes, ImmunoglobulinGenes, RAG-1Germinal CenterHomeodomain ProteinsImmunizationImmunoglobulin Class SwitchingLymphocyte ActivationMiceMice, Inbred C57BLPolymerase Chain ReactionProtein BiosynthesisProteinsVDJ RecombinasesConceptsGerminal center B cellsAntigen receptor genesT cell antigen receptor genesRAG2 proteinsB cellsRAG2 geneRAG genesRAG2 expressionFunctional immunoglobulinPeyer's patch germinal centersMessenger RNAGenesRAG1Receptor geneActivated B cellsNormal adult animalsLymphocyte populationsImmature lymphocytesGerminal centersBone marrowMurine splenicAntibody repertoireCellsAdult animalsExpression