2021
Structural visualization of transcription activated by a multidrug-sensing MerR family regulator
Yang Y, Liu C, Zhou W, Shi W, Chen M, Zhang B, Schatz DG, Hu Y, Liu B. Structural visualization of transcription activated by a multidrug-sensing MerR family regulator. Nature Communications 2021, 12: 2702. PMID: 33976201, PMCID: PMC8113463, DOI: 10.1038/s41467-021-22990-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsBacterial ProteinsBase SequenceBinding SitesCloning, MolecularCryoelectron MicroscopyCrystallography, X-RayDNA, BacterialDNA-Binding ProteinsDNA-Directed RNA PolymerasesEscherichia coliGene ExpressionGene Expression Regulation, BacterialGenetic VectorsModels, MolecularNucleic Acid ConformationPromoter Regions, GeneticProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsRecombinant ProteinsTranscription Elongation, GeneticTranscription Initiation, GeneticConceptsMerR family regulatorsFamily regulatorCryo-electron microscopy structureBacterial RNA polymerase holoenzymeRegulation of transcriptionRNA polymerase holoenzymePromoter openingTranscription regulationMicroscopy structureTranscription initiationPolymerase holoenzymeRNA elongationTranscriptional regulatorsMerR familyDNA remodelingSpacer DNAPromoter recognitionPromoter elementsCellular signalsSpacer promoterInitial transcriptionTranscription processTranscriptionPromoterRegulator
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
RAG Represents a Widespread Threat to the Lymphocyte Genome
Teng G, Maman Y, Resch W, Kim M, Yamane A, Qian J, Kieffer-Kwon KR, Mandal M, Ji Y, Meffre E, Clark MR, Cowell LG, Casellas R, Schatz DG. RAG Represents a Widespread Threat to the Lymphocyte Genome. Cell 2015, 162: 751-765. PMID: 26234156, PMCID: PMC4537821, DOI: 10.1016/j.cell.2015.07.009.Peer-Reviewed Original ResearchConceptsRecombination signalsStrong recombination signalGenome stabilityHuman genomeActive promotersGenomeDNA damageChromosomal translocationsCleavage siteWidespread threatRAG1Lymphocyte genomeEvolutionary struggleRecombinationRAGChromatinPromoterEndonucleaseSitesRAG2TranslocationAbundanceDepletionEnhancerHeptamer
2014
Targeting Of Somatic Hypermutation By immunoglobulin Enhancer And Enhancer-Like Sequences
Buerstedde JM, Alinikula J, Arakawa H, McDonald JJ, Schatz DG. Targeting Of Somatic Hypermutation By immunoglobulin Enhancer And Enhancer-Like Sequences. PLOS Biology 2014, 12: e1001831. PMID: 24691034, PMCID: PMC3972084, DOI: 10.1371/journal.pbio.1001831.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesBinding SitesB-LymphocytesCell LineChickensCytidine DeaminaseE-Box ElementsEnhancer Elements, GeneticGene Knockout TechniquesGreen Fluorescent ProteinsHumansImmunoglobulin kappa-ChainsImmunoglobulin lambda-ChainsLymphocyte ActivationMEF2 Transcription FactorsMiceMutationNF-kappa BSequence AlignmentSomatic Hypermutation, ImmunoglobulinTranscription, GeneticUracil-DNA GlycosidaseConceptsSomatic hypermutationIg enhancersNovel regulatory functionStimulation of transcriptionEnhancer-like elementCytidine deaminase proteinEnhancer-like sequenceActivation-induced cytidine deaminase proteinGene specificityTranscriptional roleHeavy chain intron enhancerTranscription unitGenetic diversityEts familyE-boxChicken cellsRegulatory functionsIntron enhancerFull activationImmunoglobulin genesTarget sequenceImmunoglobulin enhancerPoint mutationsEnhancerTranscription
2013
A Critical Context-Dependent Role for E Boxes in the Targeting of Somatic Hypermutation
McDonald JJ, Alinikula J, Buerstedde JM, Schatz DG. A Critical Context-Dependent Role for E Boxes in the Targeting of Somatic Hypermutation. The Journal Of Immunology 2013, 191: 1556-1566. PMID: 23836058, PMCID: PMC3735716, DOI: 10.4049/jimmunol.1300969.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBinding SitesCells, CulturedChickensCytidine DeaminaseDNA, RecombinantE-Box ElementsEnhancer Elements, GeneticGenes, Immunoglobulin Light ChainGenes, ReporterGreen Fluorescent ProteinsImmunoglobulin Variable RegionMutationProtein BindingSomatic Hypermutation, ImmunoglobulinTranscription Factor 3TransfectionTransgenesConceptsE-boxSomatic hypermutationChicken DT40 B cellsDT40 B cellsNon-Ig lociOff-target mutationsActivation-induced cytidine deaminaseContext-dependent roleShort DNA sequencesSequence motifsDNA sequencesTarget genesIg genesSequence contextAffinity of AbsDNA damageCytidine deaminaseRepertoire diversificationMutationsGenesMotifSequenceFunctional hierarchyHypermutationAg stimulationMultiple 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
2003
DNA mismatches and GC‐rich motifs target transposition by the RAG1/RAG2 transposase
Tsai C, Chatterji M, Schatz DG. DNA mismatches and GC‐rich motifs target transposition by the RAG1/RAG2 transposase. Nucleic Acids Research 2003, 31: 6180-6190. PMID: 14576304, PMCID: PMC275461, DOI: 10.1093/nar/gkg819.Peer-Reviewed Original ResearchRegulation of RAG1/RAG2‐mediated transposition by GTP and the C‐terminal region of RAG2
Tsai C, Schatz DG. Regulation of RAG1/RAG2‐mediated transposition by GTP and the C‐terminal region of RAG2. The EMBO Journal 2003, 22: 1922-1930. PMID: 12682024, PMCID: PMC154477, DOI: 10.1093/emboj/cdg185.Peer-Reviewed Original ResearchConceptsFull-length RAG2RAG2 proteinsRegulatory mechanismsC-terminal regionRAG proteinsHybrid joint formationDNA recognitionDNA transpositionCleavage functionChromosomal translocationsGTPUnknown mechanismRAG2ProteinTarget DNAPhysiological concentrationsRegulationJoint formationRAGRAG1MechanismTranslocationDNAGuanineTransposition
2002
RAG1-DNA Binding in V(D)J Recombination SPECIFICITY AND DNA-INDUCED CONFORMATIONAL CHANGES REVEALED BY FLUORESCENCE AND CD SPECTROSCOPY*
Ciubotaru M, Ptaszek LM, Baker GA, Baker SN, Bright FV, Schatz DG. RAG1-DNA Binding in V(D)J Recombination SPECIFICITY AND DNA-INDUCED CONFORMATIONAL CHANGES REVEALED BY FLUORESCENCE AND CD SPECTROSCOPY*. Journal Of Biological Chemistry 2002, 278: 5584-5596. PMID: 12488446, DOI: 10.1074/jbc.m209758200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBinding SitesCircular DichroismCloning, MolecularDNADNA NucleotidyltransferasesDNA-Binding ProteinsEscherichia coliGenes, RAG-1Homeodomain ProteinsKineticsMiceOligodeoxyribonucleotidesProtein ConformationRecombinant ProteinsRecombination, GeneticSubstrate SpecificityTransfectionTransposasesVDJ RecombinasesConceptsRecombination signal sequencesConformational changesSynaptic complex formationAbsence of DNAAssembly of immunoglobulinMajor conformational changesIntrinsic protein fluorophoresProtein intrinsic fluorescenceSolvent-exposed environmentRAG2 proteinsRAG1/2 complexSingle DNA moleculesRAG1 proteinSignal sequenceAcrylamide quenching studiesT-cell receptor genesStrep-tagRecombination specificityDNA moleculesProtein fluorophoresRAG1Receptor geneProteinIntrinsic fluorescenceCircular dichroism
2000
Identification of Two Catalytic Residues in RAG1 that Define a Single Active Site within the RAG1/RAG2 Protein Complex
Fugmann S, Villey I, Ptaszek L, Schatz D. Identification of Two Catalytic Residues in RAG1 that Define a Single Active Site within the RAG1/RAG2 Protein Complex. Molecular Cell 2000, 5: 97-107. PMID: 10678172, DOI: 10.1016/s1097-2765(00)80406-2.Peer-Reviewed Original ResearchConceptsActive siteDivalent metal ionsSingle active siteMetal ionsTransfer reactionsActive site regionProtein complexesBond breakageCatalysisCatalytic functionRegion of RAG1Strand transfer reactionSecondary structure prediction algorithmsAspartic acid residuesCatalytic residuesRAG2 proteinsComplexesStructure prediction algorithmsPossible structural similaritySite regionAcid residuesRetroviral integrasesRAG1Structural similarityIons
1999
Detection of RAG Protein-V(D)J Recombination Signal Interactions Near the Site of DNA Cleavage by UV Cross-Linking
Eastman Q, Villey I, Schatz D. Detection of RAG Protein-V(D)J Recombination Signal Interactions Near the Site of DNA Cleavage by UV Cross-Linking. Molecular And Cellular Biology 1999, 19: 3788-3797. PMID: 10207102, PMCID: PMC84213, DOI: 10.1128/mcb.19.5.3788.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesRAG proteinsRAG2 proteinsDNA cleavageHeptamer elementSite of cleavageActive site organizationRAG1-RAG2RAG1 proteinSignal sequenceDouble-strand cleavageSite-specific interactionsSame nucleotideRecognition surfaceProteinRAG1UV CrossSignal interactionsSite organizationCleavageSequenceComplexesSitesClose proximityNucleotides
1998
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system
Agrawal A, Eastman Q, Schatz D. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 1998, 394: 744-751. PMID: 9723614, DOI: 10.1038/29457.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodiesBinding SitesB-LymphocytesCatalysisCell LineDNADNA Transposable ElementsDNA, CircularDNA-Binding ProteinsDrug Resistance, MicrobialEvolution, MolecularGene Rearrangement, B-LymphocyteGene Rearrangement, T-LymphocyteHigh Mobility Group ProteinsHomeodomain ProteinsImmune SystemMiceMolecular Sequence DataReceptors, Antigen, T-CellRecombination, GeneticRestriction MappingTransposasesVertebratesConceptsT-cell receptor genesRecombination signalsSequence-specific DNA recognitionAncestral receptor geneComponent gene segmentsSite-specific recombination reactionPiece of DNAEvolutionary divergenceJawless vertebratesRecombination-activating geneTransposable elementsDNA recognitionRetroviral integrationGermline insertionDNA moleculesGenesShort duplicationsDNA cleavageRAG1Gene segmentsTransposition reactionRAG2Receptor geneTarget DNA moleculesTarget DNA
1997
Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster
Bellon S, Rodgers K, Schatz D, Coleman J, Steitz T. Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster. Nature Structural & Molecular Biology 1997, 4: 586-591. PMID: 9228952, DOI: 10.1038/nsb0797-586.Peer-Reviewed Original Research
1996
A Zinc-binding Domain Involved in the Dimerization of RAG1
Rodgers K, Bu Z, Fleming K, Schatz D, Engelman D, Coleman J. A Zinc-binding Domain Involved in the Dimerization of RAG1. Journal Of Molecular Biology 1996, 260: 70-84. PMID: 8676393, DOI: 10.1006/jmbi.1996.0382.Peer-Reviewed Original ResearchConceptsRecombination-activating gene 1Zinc-binding motifDimerization domainZinc fingerProtein-protein interactionsLymphoid-specific genesN-terminal thirdZinc finger sequencesAmino acid residuesC3HC4 motifRAG1 sequencesRAG1 proteinTerminal domainHomodimer formationAcid residuesBiophysical techniquesGene 1Energetics of associationMonomeric subunitsMotifProteinFinger sequencesSequenceC3HC4Zinc ions