2015
Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes
Hu J, Zhang Y, Zhao L, Frock RL, Du Z, Meyers RM, Meng FL, Schatz DG, Alt FW. Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes. Cell 2015, 163: 947-959. PMID: 26593423, PMCID: PMC4660266, DOI: 10.1016/j.cell.2015.10.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCCCTC-Binding FactorChromosomes, MammalianDNA-Binding ProteinsGenes, mycGenomeHigh-Throughput Nucleotide SequencingHomeodomain ProteinsHumansImmunoglobulin Heavy ChainsLymphomaMiceNucleotide MotifsRegulatory Sequences, Nucleic AcidRepressor ProteinsSequence Analysis, DNATranslocation, GeneticV(D)J RecombinationConceptsRecombination signal sequencesRSS pairAntigen receptor genesSignal sequenceRAG activityDNA breaksChromosomal loopsLoop domainBiological processesConvergent CTCFChromosomal translocationsCleavage siteReceptor geneTarget activitySuch breaksMarked orientation dependenceRecombinationRAGCTCFChromatinMegabasesOff-target distributionGenesBreaksDomain
2012
Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions
Subrahmanyam R, Du H, Ivanova I, Chakraborty T, Ji Y, Zhang Y, Alt FW, Schatz DG, Sen R. Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions. Nature Immunology 2012, 13: 1205-1212. PMID: 23104096, PMCID: PMC3685187, DOI: 10.1038/ni.2447.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCell LineChromatinEpigenesis, GeneticGene Rearrangement, B-Lymphocyte, Heavy ChainGenes, Immunoglobulin Heavy ChainHistonesImmunoglobulin Heavy ChainsImmunoglobulin Joining RegionImmunoglobulin Variable RegionMicePrecursor Cells, B-LymphoidRecombinasesRecombination, GeneticAID-Targeting and Hypermutation of Non-Immunoglobulin Genes Does Not Correlate with Proximity to Immunoglobulin Genes in Germinal Center B Cells
Gramlich HS, Reisbig T, Schatz DG. AID-Targeting and Hypermutation of Non-Immunoglobulin Genes Does Not Correlate with Proximity to Immunoglobulin Genes in Germinal Center B Cells. PLOS ONE 2012, 7: e39601. PMID: 22768095, PMCID: PMC3387148, DOI: 10.1371/journal.pone.0039601.Peer-Reviewed Original ResearchConceptsNon-Ig genesC-MycIg genesAID targetingGerminal center B cellsDouble-strand break endsImportant regulatory elementsNon-immunoglobulin genesMYC transgeneHeavy chain geneRegulatory elementsBreak endsIg heavy chain genesIg lociHuman MYCGenesB cellsSuch translocationsImmunoglobulin lociImmunoglobulin genesTranslocation partnersChain geneHuman Burkitt lymphomaSomatic hypermutationNuclear position
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
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 activation
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 ResearchB 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 rearrangement
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
2001
Factors and Forces Controlling V(D)J Recombination
Hesslein D, Schatz D. Factors and Forces Controlling V(D)J Recombination. Advances In Immunology 2001, 78: 169-232. PMID: 11432204, DOI: 10.1016/s0065-2776(01)78004-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
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