2021
Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination
Chen CC, Chen BR, Wang Y, Curman P, Beilinson HA, Brecht RM, Liu CC, Farrell RJ, de Juan-Sanz J, Charbonnier LM, Kajimura S, Ryan TA, Schatz DG, Chatila TA, Wikstrom JD, Tyler JK, Sleckman BP. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination. Journal Of Experimental Medicine 2021, 218: e20201708. PMID: 34033676, PMCID: PMC8155808, DOI: 10.1084/jem.20201708.Peer-Reviewed Original ResearchConceptsRAG2 gene expressionSarco/endoplasmic reticulum Ca2Gene expressionEndoplasmic reticulum Ca2ER Ca2ER transmembrane proteinExpression of SERCA3Mature B cellsER lumenCytosolic Ca2Transmembrane proteinCRISPR/PreB cellsDNA cleavageB cellsReticulum Ca2SERCA proteinATPase activityProteinProfound blockATP2A2 mutationsRAG1Recombination
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
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
Mapping and Quantitation of the Interaction between the Recombination Activating Gene Proteins RAG1 and RAG2* ♦
Zhang YH, Shetty K, Surleac MD, Petrescu AJ, Schatz DG. Mapping and Quantitation of the Interaction between the Recombination Activating Gene Proteins RAG1 and RAG2* ♦. Journal Of Biological Chemistry 2015, 290: 11802-11817. PMID: 25745109, PMCID: PMC4424321, DOI: 10.1074/jbc.m115.638627.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCatalytic DomainDNA-Binding ProteinsGene Expression RegulationGenome, HumanHEK293 CellsHomeodomain ProteinsHumansInterferometryMaleMiceMice, Inbred C57BLMolecular Sequence DataMutationNuclear ProteinsProtein BindingProtein Interaction MappingProtein Structure, SecondaryThymus GlandV(D)J RecombinationVDJ RecombinasesConceptsRegion of RAG1Α-helixZinc finger regionResidues N-terminalActive siteAcidic amino acidsPulldown assaysAccessory factorsHermes transposaseProteins RAG1Finger regionRAG activityQuantitative Western blottingC-terminusRAG endonucleaseN-terminalCatalytic functionRAG1Amino acidsDNA cleavageRAG2Nuclear concentrationRecombination activityCatalytic centerBiolayer interferometry
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
Sin1-mTORC2 Suppresses rag and il7r Gene Expression through Akt2 in B Cells
Lazorchak AS, Liu D, Facchinetti V, Di Lorenzo A, Sessa WC, Schatz DG, Su B. Sin1-mTORC2 Suppresses rag and il7r Gene Expression through Akt2 in B Cells. Molecular Cell 2010, 39: 433-443. PMID: 20705244, PMCID: PMC2957800, DOI: 10.1016/j.molcel.2010.07.031.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsB-LymphocytesCell Line, TransformedDNA-Binding ProteinsForkhead Box Protein O1Forkhead Transcription FactorsGene Expression RegulationGene Rearrangement, B-LymphocyteHomeodomain ProteinsMiceMice, KnockoutPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, Interleukin-7Signal TransductionTOR Serine-Threonine KinasesTranscription FactorsConceptsB cell developmentGene expressionCell developmentRAG gene expressionMTOR complex 2FOXO1 transcriptional activityPI3K signalingMTOR inhibitor rapamycinTranscriptional activityKey regulatorB cellsMolecular mechanismsInhibitor rapamycinK signalingCell survivalFoxO1 phosphorylationMammalian targetRecombinase activityPI3KIL-7 receptorAkt2SignalingRapamycinExpressionCells
2006
Roles of the Ig κ Light Chain Intronic and 3′ Enhancers in Igk Somatic Hypermutation
Inlay MA, Gao HH, Odegard VH, Lin T, Schatz DG, Xu Y. Roles of the Ig κ Light Chain Intronic and 3′ Enhancers in Igk Somatic Hypermutation. The Journal Of Immunology 2006, 177: 1146-1151. PMID: 16818772, DOI: 10.4049/jimmunol.177.2.1146.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAnimalsB-LymphocytesCells, CulturedDown-RegulationEnhancer Elements, GeneticGene DeletionGene Expression RegulationGerminal CenterImmunoglobulin kappa-ChainsIntronsLymphocyte ActivationMiceMice, KnockoutMice, TransgenicRNA, MessengerSomatic Hypermutation, ImmunoglobulinSpleen
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 activationInducible Gene Expression Using an Autoregulatory, Tetracycline‐Controlled System
Shockett P, Schatz D. Inducible Gene Expression Using an Autoregulatory, Tetracycline‐Controlled System. Current Protocols In Cell Biology 2005, 27: 20.8.1-20.8.10. PMID: 18228465, DOI: 10.1002/0471143030.cb2008s27.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene Expression RegulationGene TargetingGenetic MarkersGenetic VectorsMiceMice, TransgenicMolecular BiologyNIH 3T3 CellsPlasmidsTetracyclineTrans-ActivatorsTransfectionConceptsInducible gene expressionSelectable markerGene expressionSecond selectable markerCell linesFibroblast cell lineTransient transfectionGene protein expressionResultant clonesStable linesMarker plasmidPlasmidProtein expressionAdherent cellsTransactivatorExpressionTransfectionCellsTargetGenesSupport protocolClonesLinesMarkersAutoregulatory
2002
Inducible Gene Expression Using an Autoregulatory, Tetracycline‐Controlled System
Shockett P, Schatz D. Inducible Gene Expression Using an Autoregulatory, Tetracycline‐Controlled System. Current Protocols In Molecular Biology 2002, 60: 16.14.1-16.14.9. PMID: 18265300, DOI: 10.1002/0471142727.mb1614s60.Peer-Reviewed Original ResearchConceptsInducible gene expressionSelectable markerGene expressionSecond selectable markerCell linesFibroblast cell lineTransient transfectionGene protein expressionResultant clonesStable linesMarker plasmidPlasmidProtein expressionAdherent cellsTransactivatorExpressionTransfectionCellsTargetGenesSupport protocolClonesLinesMarkersAutoregulatoryInducible, reversible hair loss in transgenic mice
Chen J, Kelz MB, Zeng G, Steffen C, Shockett PE, Terwilliger G, Schatz DG, Nestler EJ. Inducible, reversible hair loss in transgenic mice. Transgenic Research 2002, 11: 241-247. PMID: 12113456, DOI: 10.1023/a:1015619604318.Peer-Reviewed Original ResearchMeSH KeywordsAlopeciaAnimalsDisease Models, AnimalDoxycyclineGene Expression RegulationMiceMice, TransgenicTetracyclineTrans-ActivatorsConceptsTelogen effluviumInducible transgenic miceHair lossTransgenic miceReversible hair lossSkin pathologyHair loss phenotypeAnimal modelsMolecular abnormalitiesDecreased numberMiceHair folliclesAnagen phaseCommon typeEffluviumTelogen phasePresent findingsLoss phenotypeFolliclesPathologyMolecular mechanismsMorphological changesReporter luciferase geneLuciferase geneHigh levels
1997
αβ Lineage‐committed thymocytes can be rescued by the γδ T cell receptor (TCR) in the absence of TCR β chain
Livák F, Wilson A, MacDonald H, Schatz D. αβ Lineage‐committed thymocytes can be rescued by the γδ T cell receptor (TCR) in the absence of TCR β chain. European Journal Of Immunology 1997, 27: 2948-2958. PMID: 9394823, DOI: 10.1002/eji.1830271130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationFemaleGene Expression RegulationGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorMiceMice, Inbred AKRMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, ImmunologicalReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaT-Lymphocyte SubsetsThymus GlandTransgenesConceptsT cell receptorLineage commitmentT cell lineage commitmentCell lineage commitmentAlpha beta T cell developmentTCR beta proteinGamma delta T cell lineagesAlpha beta lineageT cell developmentCell receptorTCR-mediated selectionGene rearrangementsCell lineagesT cellsΑβ lineageCell developmentTCR gammaAlpha betaT-cell lineageBeta lineageLineagesGamma delta T-cell receptorTCR β chainGamma delta T cellsDelta T-cell receptorSwitching on gene expression
Shockett P, Schatz D. Switching on gene expression. Nature Biotechnology 1997, 15: 219-221. PMID: 9062915, DOI: 10.1038/nbt0397-219.Commentaries, Editorials and LettersAnimalsGene Expression RegulationHuman Growth HormoneMiceMice, KnockoutMice, TransgenicMifepristoneTetracycline
1996
Diverse strategies for tetracycline-regulated inducible gene expression.
Shockett PE, Schatz DG. Diverse strategies for tetracycline-regulated inducible gene expression. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 5173-5176. PMID: 8643548, PMCID: PMC39217, DOI: 10.1073/pnas.93.11.5173.Peer-Reviewed Original ResearchAnimalsBeta-GalactosidaseCytomegalovirusEscherichia coliGene Expression RegulationHumansRepressor ProteinsTetracyclineThe half-life of RAG-1 protein in precursor B cells is increased in the absence of RAG-2 expression.
Grawunder U, Schatz DG, Leu TM, Rolink A, Melchers F. The half-life of RAG-1 protein in precursor B cells is increased in the absence of RAG-2 expression. Journal Of Experimental Medicine 1996, 183: 1731-1737. PMID: 8666930, PMCID: PMC2192496, DOI: 10.1084/jem.183.4.1731.Peer-Reviewed Original Research
1995
A modified tetracycline-regulated system provides autoregulatory, inducible gene expression in cultured cells and transgenic mice.
Shockett P, Difilippantonio M, Hellman N, Schatz DG. A modified tetracycline-regulated system provides autoregulatory, inducible gene expression in cultured cells and transgenic mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 6522-6526. PMID: 7604026, PMCID: PMC41550, DOI: 10.1073/pnas.92.14.6522.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsBlotting, WesternCells, CulturedDNA NucleotidyltransferasesGene Expression RegulationHerpes Simplex Virus Protein Vmw65MiceMice, TransgenicOpen Reading FramesPlasmidsRecombinant Fusion ProteinsRepressor ProteinsRestriction MappingRNA, MessengerSequence DeletionTetracyclineTrans-ActivatorsTransfectionVDJ RecombinasesConceptsInducible gene expressionGene expressionTetracycline-regulated gene expressionTranscriptional activation domainCultured cellsTetracycline-regulated systemTransgenic miceExpression of tTAAutoregulatory systemActivation domainTTA geneInducible promoterTetracycline repressorInducible expressionFusion proteinTransactivator proteinConstitutive expressionTransgenic animalsGene 1Induced levelsRecombination activityMost tissuesConstitutive systemProteinCell lines
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 KeywordsActinsAnimalsB-LymphocytesBlotting, NorthernBursa 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
1989
The V(D)J recombination activating gene, RAG-1
Schatz D, Oettinger M, Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell 1989, 59: 1035-1048. PMID: 2598259, DOI: 10.1016/0092-8674(89)90760-5.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological EvolutionCell LineCloning, MolecularDNA NucleotidyltransferasesGene Expression RegulationGene LibraryGene Rearrangement, T-LymphocyteGenes, ImmunoglobulinGenomic LibraryHumansMiceMolecular Sequence DataNucleic Acid HybridizationOligonucleotide ProbesReceptors, Antigen, T-CellRecombination, GeneticSequence Homology, Nucleic AcidT-LymphocytesTransfectionVDJ Recombinases