2016
RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2
Maman Y, Teng G, Seth R, Kleinstein SH, Schatz DG. RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2. Nucleic Acids Research 2016, 44: 9624-9637. PMID: 27436288, PMCID: PMC5175335, DOI: 10.1093/nar/gkw633.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesChromatinChromatin ImmunoprecipitationGenomeGenomic InstabilityHigh-Throughput Nucleotide SequencingHistonesHomeodomain ProteinsHumansMiceNucleotide MotifsPromoter Regions, GeneticProtein BindingProtein Interaction Domains and MotifsRecombination, GeneticV(D)J RecombinationConceptsAntigen receptor lociNon-core regionsReceptor locusPlant homeodomain (PHD) fingerChIP-seq dataWide bindingChromatin interactionsAdditional chromatinLysine 4Off-target activityGenomic featuresHistone 3Novel roleRAG1LociChromatinGenomeRAG2Observed patternsDistinct modesBindingH3K4me3H3K27acEndonucleaseRelative contribution
2013
Higher-Order Looping and Nuclear Organization of Tcra Facilitate Targeted RAG Cleavage and Regulated Rearrangement in Recombination Centers
Chaumeil J, Micsinai M, Ntziachristos P, Deriano L, Wang J, Ji Y, Nora EP, Rodesch MJ, Jeddeloh JA, Aifantis I, Kluger Y, Schatz DG, Skok JA. Higher-Order Looping and Nuclear Organization of Tcra Facilitate Targeted RAG Cleavage and Regulated Rearrangement in Recombination Centers. Cell Reports 2013, 3: 359-370. PMID: 23416051, PMCID: PMC3664546, DOI: 10.1016/j.celrep.2013.01.024.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell NucleusDNA DamageDNA-Binding ProteinsGenetic LociGenomic InstabilityHistonesHomeodomain ProteinsMiceMice, Inbred C57BLMice, Inbred CBAMice, KnockoutProtein Serine-Threonine KinasesReceptors, Antigen, T-Cell, alpha-betaTumor Suppressor ProteinsV(D)J RecombinationConceptsAntigen receptor lociRegulated rearrangementsGenome stabilityNuclear organizationRAG cleavageRAG recombinaseNuclear accessibilityRAG bindingCellular transformationΑ locusRecombination eventsReceptor locusDiverse arrayCell receptorLociLoop formationTight controlRegulationCleavageFocal bindingGenetic anomaliesBindingKey determinantRearrangementTranscriptionThe Ataxia Telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements
Steinel NC, Lee BS, Tubbs AT, Bednarski JJ, Schulte E, Yang-Iott KS, Schatz DG, Sleckman BP, Bassing CH. The Ataxia Telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements. Journal Of Experimental Medicine 2013, 210: 233-239. PMID: 23382544, PMCID: PMC3570110, DOI: 10.1084/jem.20121605.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAllelesAnimalsAtaxia Telangiectasia Mutated ProteinsBase SequenceB-LymphocytesCell Cycle ProteinsDNA Breaks, Double-StrandedDNA-Binding ProteinsGene Rearrangement, B-Lymphocyte, Light ChainHistonesHomeodomain ProteinsImmunoglobulin kappa-ChainsIntracellular Signaling Peptides and ProteinsMiceMice, 129 StrainMice, KnockoutModels, BiologicalProtein Serine-Threonine KinasesRNA, MessengerSignal TransductionTumor Suppressor ProteinsConceptsDNA double-strand breaksRAG DNA double-strand breaksAllelic exclusionIgκ rearrangementAtaxia telangiectasiaProtein kinase kinaseAntigen receptor chainsDouble-strand breaksHistone H2AX phosphorylationFeedback inhibitionATM kinaseIgκ recombinationKinase kinaseDNA-PKConcomitant repressionH2AX phosphorylationRAG endonucleaseReceptor chainsMDC1H2AXKinaseAllelesRecombinationRearrangementTelangiectasia
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, GeneticA Dual Interaction between the DNA Damage Response Protein MDC1 and the RAG1 Subunit of the V(D)J Recombinase*
Coster G, Gold A, Chen D, Schatz DG, Goldberg M. A Dual Interaction between the DNA Damage Response Protein MDC1 and the RAG1 Subunit of the V(D)J Recombinase*. Journal Of Biological Chemistry 2012, 287: 36488-36498. PMID: 22942284, PMCID: PMC3476314, DOI: 10.1074/jbc.m112.402487.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid MotifsBRCA1 ProteinCell Cycle ProteinsCell Line, TumorHistonesHomeodomain ProteinsHumansModels, BiologicalNuclear ProteinsPeptide MappingPhosphorylationProtein Structure, TertiaryRepetitive Sequences, Amino AcidTrans-ActivatorsVDJ RecombinasesConceptsDNA double-strand breaksDNA damage responseTandem BRCA1 C-terminal (BRCT) domainsC-terminusSpecific DNA double-strand breaksBRCA1 C-terminal domainC-terminal domainThreonine-rich repeatsDouble-strand breaksRAG1 subunitRAG recombinaseRAG2 proteinsDDR proteinsDamage responseRegulatory signalsBinding interfaceBreak siteHistone H2AXRAG activityRich repeatsNon-core regionsMDC1RAG1PhosphorylationSubsequent signal amplification
2010
Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination
Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, Schatz DG. Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. Journal Of Experimental Medicine 2010, 207: 2809-2816. PMID: 21115692, PMCID: PMC3005232, DOI: 10.1084/jem.20101136.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBinding, CompetitiveChromatin ImmunoprecipitationDNAEnhancer Elements, GeneticFemaleGene RearrangementGenes, ImmunoglobulinGenotypeHistonesHMGB1 ProteinHomeodomain ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticProtein BindingReceptors, Antigen, T-Cell, alpha-betaRecombination, GeneticTranscription, GeneticVDJ Recombinases
2006
Targeting of somatic hypermutation
Odegard VH, Schatz DG. Targeting of somatic hypermutation. Nature Reviews Immunology 2006, 6: 573-583. PMID: 16868548, DOI: 10.1038/nri1896.Peer-Reviewed Original Research
2005
Histone 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
B 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