2024
RORγt up-regulates RAG gene expression in DP thymocytes to expand the Tcra repertoire
Naik A, Dauphars D, Corbett E, Simpson L, Schatz D, Krangel M. RORγt up-regulates RAG gene expression in DP thymocytes to expand the Tcra repertoire. Science Immunology 2024, 9: eadh5318. PMID: 38489350, PMCID: PMC11005092, DOI: 10.1126/sciimmunol.adh5318.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene ExpressionMiceNuclear Receptor Subfamily 1, Group F, Member 3Receptors, Antigen, T-Cell, alpha-betaThymocytesTranscription FactorsConceptsRecombination activating geneDP thymocytesUp-regulatedAntigen receptor lociDouble-positive (DP) stageRAG expressionTranscriptional up-regulationDouble-negative (DNRAG gene expressionActive genesTcra repertoireReceptor locusDN thymocytesGene expressionThymocyte transitionLymphocyte developmentThymocyte proliferationPhysiological importanceMultiple pathwaysRORgtThymocytesExpressionRepertoireRecombinationAntisilencing
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 ResearchMeSH KeywordsAnimalsChickensGenes, ImmunoglobulinHumansSomatic Hypermutation, ImmunoglobulinTranscription FactorsConceptsActivation-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
2013
Multiple Transcription Factor Binding Sites Predict AID Targeting in Non-Ig Genes
Duke JL, Liu M, Yaari G, Khalil AM, Tomayko MM, Shlomchik MJ, Schatz DG, Kleinstein SH. Multiple Transcription Factor Binding Sites Predict AID Targeting in Non-Ig Genes. The Journal Of Immunology 2013, 190: 3878-3888. PMID: 23514741, PMCID: PMC3689293, DOI: 10.4049/jimmunol.1202547.Peer-Reviewed Original ResearchConceptsTranscription Factor Binding SitesAID-induced lesionsNon-Ig genesGenome instabilityTranscription factorsAberrant targetingSequence dataCertain genesGenesAID targetingGerminal center B cellsSomatic mutationsLikely targetBinding sitesAID targetsTargetingClassification tree modelMistargetingB cellsLociMechanismTargetMutationsSites
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
2004
Pax5-Deficient Mice Exhibit Early Onset Osteopenia with Increased Osteoclast Progenitors
Horowitz MC, Xi Y, Pflugh DL, Hesslein DG, Schatz DG, Lorenzo JA, Bothwell AL. Pax5-Deficient Mice Exhibit Early Onset Osteopenia with Increased Osteoclast Progenitors. The Journal Of Immunology 2004, 173: 6583-6591. PMID: 15557148, DOI: 10.4049/jimmunol.173.11.6583.Peer-Reviewed Original ResearchConceptsNumber of osteoclastsSpleen cellsB cellsOsteoclast developmentB cell-deficient miceCell-deficient miceControl spleen cellsB lymphocyte lineage cellsBone marrow cellsB-cell lineagePro-B cell stageMonocyte phenotypeBone massOsteoclast precursorsMice exhibitOsteoclast progenitorsMarrow cellsGrowth factorMiceOsteoclastsLineage cellsOsteopeniaCell lineagesCellsAdherent cellsB 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 rearrangementUp-Regulation of Hlx in Immature Th Cells Induces IFN-γ Expression
Zheng WP, Zhao Q, Zhao X, Li B, Hubank M, Schatz DG, Flavell RA. Up-Regulation of Hlx in Immature Th Cells Induces IFN-γ Expression. The Journal Of Immunology 2004, 172: 114-122. PMID: 14688316, DOI: 10.4049/jimmunol.172.1.114.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAdoptive TransferAnimalsCD4-Positive T-LymphocytesCell DifferentiationCells, CulturedHemocyaninsHomeodomain ProteinsInjections, IntravenousInjections, SubcutaneousInterferon-gammaInterphaseMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicTh1 CellsT-Lymphocytes, Helper-InducerTranscription FactorsUp-RegulationConceptsCD4 T cellsTransgenic CD4 T cellsTh2-polarizing conditionsTh1 cell differentiationTh cellsT cellsTh1 cellsIFN-gammaKeyhole limpet hemocyanin immunizationNormal CD4 T cellsTime pointsIntracellular cytokine stainingIFN-γ expressionIFN-gamma expressionEarly time pointsCytokine stainingTh2 cellsNaive precursorsCell differentiationSpecific time pointsThymocyte populationTransgenic miceMarked reductionAberrant expressionRetroviral infection
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