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 ResearchConceptsRecombination 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 pathwaysRORgtThymocytesExpressionRepertoireRecombinationAntisilencingChapter 2 The Mechanism, Regulation and Evolution of V(D)J Recombination
Schatz D, Zhang Y, Xiao J, Zha S, Zhang Y, Alt F. Chapter 2 The Mechanism, Regulation and Evolution of V(D)J Recombination. 2024, 13-57. DOI: 10.1016/b978-0-323-95895-0.00004-0.Peer-Reviewed Original ResearchAntigen receptor lociNon-homologous end joiningChromatin loop extrusionRecombination-activating geneLoop extrusionV(D)J recombinationRecombination-activating gene proteinV(D)J recombination reactionReceptor locusEnd joiningDouble-strand (ds) DNA breaksLoop extrusion mechanismRegulation of recombinationRepertoire of antigen receptorsLymphocyte developmentOncogenic chromosomal translocationsVariable region gene segmentsDNA repair proteinsDNA repair pathwaysChromatin accessibilityDNA segmentsV(D)J recombinase activitySubstrate DNALoop domainV(D)J junctions
2020
Nucleolar localization of RAG1 modulates V(D)J recombination activity
Brecht RM, Liu CC, Beilinson HA, Khitun A, Slavoff SA, Schatz DG. Nucleolar localization of RAG1 modulates V(D)J recombination activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 4300-4309. PMID: 32047031, PMCID: PMC7049140, DOI: 10.1073/pnas.1920021117.Peer-Reviewed Original ResearchConceptsNucleolar localizationProximity-dependent biotin identificationRecombination activityDisruption of nucleoliDiscrete gene segmentsAntigen receptor lociPre-B cell linesNegative regulatory mechanismsN-terminal regionAmino acids 216Biotin identificationLocalization motifNucleolar associationProtein complexesNucleolar proteinsNucleolar sequestrationT-cell receptor genesRegulatory mechanismsNucleolar markerReceptor locusEfficient egressRAG1Amino acidsGene segmentsReceptor gene
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
2015
Chapter One Regulation and Evolution of the RAG Recombinase
Teng G, Schatz DG. Chapter One Regulation and Evolution of the RAG Recombinase. Advances In Immunology 2015, 128: 1-39. PMID: 26477364, DOI: 10.1016/bs.ai.2015.07.002.Peer-Reviewed Original ResearchConceptsRAG activityOverall genome integrityDNA breakageSpecific DNA motifsAntigen receptor lociDNA repair pathwaysChapter One RegulationAntigen receptor genesEarly lymphocyte developmentCell cycle statusGenome integrityChromatin structureRAG recombinaseRAG2 proteinsDNA motifsSpatial regulationWidespread bindingRepair pathwaysDNA cleavage activityRecombination eventsShuffling reactionEnzymatic potentialRAG endonucleaseReceptor locusLymphocyte developmentChapter 2 The Mechanism of V(D)J Recombination
Little A, Matthews A, Oettinger M, Roth D, Schatz D. Chapter 2 The Mechanism of V(D)J Recombination. 2015, 13-34. DOI: 10.1016/b978-0-12-397933-9.00002-3.ChaptersLymphocyte developmentNonhomologous end-joining pathwayRegulation of recombinationAntigen receptor lociEnd-joining pathwayDNA repair proteinsRecombination-activating gene 1RAG proteinsDNA breaksRecombinase machineryFunctional antigen receptorEnd processingReceptor locusGenetic instabilityGene 1Recombinase activityChromosomal translocationsDNA cleavageProtein 1Diverse repertoireRepair stepsBox protein 1Antigen receptorHigh mobility group box protein 1Recombination
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 determinantRearrangementTranscription
2011
Recombination centres and the orchestration of V(D)J recombination
Schatz DG, Ji Y. Recombination centres and the orchestration of V(D)J recombination. Nature Reviews Immunology 2011, 11: 251-263. PMID: 21394103, DOI: 10.1038/nri2941.Peer-Reviewed Original ResearchConceptsAntigen receptor genesRecombination signal sequencesSignal sequenceHigher-order chromatin architectureHistone H3 lysine 4Receptor geneAntigen receptor gene segmentsInactive nuclear compartmentsPlant homeodomain (PHD) fingerH3 lysine 4Antigen receptor lociReceptor gene segmentsEctopic recruitmentChromatin architectureChromatin structureLysine 4Active chromatinGenome instabilityHistone modificationsRAG2 proteinsThousands of sitesNuclear compartmentRecombination eventsTranscriptional activityGenomic DNA
2010
The In Vivo Pattern of Binding of RAG1 and RAG2 to Antigen Receptor Loci
Ji Y, Resch W, Corbett E, Yamane A, Casellas R, Schatz DG. The In Vivo Pattern of Binding of RAG1 and RAG2 to Antigen Receptor Loci. Cell 2010, 141: 419-431. PMID: 20398922, PMCID: PMC2879619, DOI: 10.1016/j.cell.2010.03.010.Peer-Reviewed Original ResearchConceptsJ gene segmentsRAG proteinsGene segmentsSignal sequenceLineage-specific mannerAntigen receptor lociRecombination signal sequencesLysine 4Active chromatinRAG2 bindThousands of sitesHistone 3Receptor locusDevelopmental stagesD gene segmentsDiscrete sitesCritical initial stepVivo patternRAG1BindingRAG2Beta JProteinRecombinationSpecific binding
2004
New concepts in the regulation of an ancient reaction: transposition by RAG1/RAG2
Chatterji M, Tsai C, Schatz DG. New concepts in the regulation of an ancient reaction: transposition by RAG1/RAG2. Immunological Reviews 2004, 200: 261-271. PMID: 15242411, DOI: 10.1111/j.0105-2896.2004.00167.x.Peer-Reviewed Original ResearchConceptsRAG proteinsRecombination-activating gene 1Transposition activityAntigen receptor lociDNA double-stand breaksRAG1/RAG2Lymphoid-specific factorsDouble-stand breaksEndonuclease activityGene 1Chromosomal translocationsVariety of mechanismsProteinSpecific sitesRAG2Ancient reactionRecombinationRecent studiesGenome