Nils Neuenkirchen, PhD
Cards
About
Research
Publications
2024
Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape
Boddu P, Gupta A, Roy R, De La Peña Avalos B, Olazabal-Herrero A, Neuenkirchen N, Zimmer J, Chandhok N, King D, Nannya Y, Ogawa S, Lin H, Simon M, Dray E, Kupfer G, Verma A, Neugebauer K, Pillai M. Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape. Molecular Cell 2024, 84: 1475-1495.e18. PMID: 38521065, PMCID: PMC11061666, DOI: 10.1016/j.molcel.2024.02.032.Peer-Reviewed Original ResearchRate of RNA polymerase IIChromatin landscapeElongation defectsElongation rate of RNA polymerase IIImpaired protein-protein interactionsSplicing of pre-messenger RNATranscription elongation defectsRNA polymerase IIProtein-protein interactionsPre-messenger RNACancer-associated mutationsIsogenic cell linesSin3/HDAC complexGene bodiesPolymerase IIChromatin accessibilityH3K4me3 markChromatin changesMutant SF3B1ChromatinMutant mouse modelsEpigenetic disordersEpigenetic factorsHuman diseasesMutant state
2023
Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E
Boddu P, Gupta A, Roy R, De La Pena Avalos B, Herrero A, Zimmer J, Simon M, Chandhok N, King D, Neuenkirchen N, Dray E, Lin H, Kupfer G, Verma A, Neugebauer K, Pillai M. Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E. Blood 2023, 142: 714. DOI: 10.1182/blood-2023-187303.Peer-Reviewed Original ResearchSplicing factorsChIP-seqK562 cell lineKey regulatory genesCell linesSingle mutant alleleNon-denaturing gelsAlternative splicingTranscriptional kineticsRegulatory genesSpliceosome assemblySplicing efficiencyMRNA splicingCRISPR/Progenitor populationsNeomorphic functionsMolecular mechanismsMutant allelesIsoform changesGene editingNovel mechanismMutationsSF mutationsRecurrent mutationsAssembly kinetics
2022
Integrative genome-wide analysis reveals EIF3A as a key downstream regulator of translational repressor protein Musashi 2 (MSI2)
Karmakar S, Ramirez O, Paul KV, Gupta AK, Kumari V, Botti V, de los Mozos IR, Neuenkirchen N, Ross RJ, Karanicolas J, Neugebauer KM, Pillai MM. Integrative genome-wide analysis reveals EIF3A as a key downstream regulator of translational repressor protein Musashi 2 (MSI2). NAR Cancer 2022, 4: zcac015. PMID: 35528200, PMCID: PMC9070473, DOI: 10.1093/narcan/zcac015.Peer-Reviewed Original ResearchRNA binding proteinMusashi-2Functional targetIntegrative genome-wide analysisGenome-wide analysisIndividual-nucleotide resolutionAsymmetric cell divisionCell fate decisionsThousands of mRNAsKey downstream regulatorProtein Musashi-2Polysome profilingFate decisionsEukaryotic translation initiation factor 3aNucleotide resolutionCell divisionDirect RNATranslational inductionCancer stem cellsDownstream regulatorsUntranslated regionIndirect targetsBinding proteinDirect targetMere bindingPrecision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies
Biancon G, Joshi P, Zimmer JT, Hunck T, Gao Y, Lessard MD, Courchaine E, Barentine AES, Machyna M, Botti V, Qin A, Gbyli R, Patel A, Song Y, Kiefer L, Viero G, Neuenkirchen N, Lin H, Bewersdorf J, Simon MD, Neugebauer KM, Tebaldi T, Halene S. Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies. Molecular Cell 2022, 82: 1107-1122.e7. PMID: 35303483, PMCID: PMC8988922, DOI: 10.1016/j.molcel.2022.02.025.Peer-Reviewed Original Research
2021
Genome-wide mapping of Piwi association with specific loci in Drosophila ovaries
Liu N, Neuenkirchen N, Zhong M, Lin H. Genome-wide mapping of Piwi association with specific loci in Drosophila ovaries. G3: Genes, Genomes, Genetics 2021, 11: jkaa059. PMID: 33609367, PMCID: PMC8022938, DOI: 10.1093/g3journal/jkaa059.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsProtein-coding genesDrosophila ovaryGermline stem cell maintenanceRole of piRNAsTermination sitesGenome-wide mappingGenomic binding profileTranscriptional termination sitesSpecific genomic sitesStem cell maintenanceRNA pathwaysTransposon repressionTranscriptional startEuchromatic regionsGene regulationEpigenetic regulationGenomic sitesCell maintenancePiwiSpecific lociMethylation signalsDiverse mechanismsTarget siteBinding sites
2018
The Role of Maternal HP1a in Early Drosophila Embryogenesis via Regulation of Maternal Transcript Production
Park AR, Liu N, Neuenkirchen N, Guo Q, Lin H. The Role of Maternal HP1a in Early Drosophila Embryogenesis via Regulation of Maternal Transcript Production. Genetics 2018, 211: 201-217. PMID: 30442760, PMCID: PMC6325692, DOI: 10.1534/genetics.118.301704.Peer-Reviewed Original ResearchConceptsHeterochromatin protein 1aMaternal transcriptsEarly Drosophila embryogenesisGermline developmentDrosophila embryogenesisMRNA splicingCell divisionTranscript productionProtein 1AEpigenetic factorsDownregulates genesEmbryogenesisGenesTranscriptsSplicingOogenesisTranscriptionOrganogenesisRegulationRoleProductionNeurogenesisDivisionDevelopmentTranslationA Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs
Wang Z, Gearhart MD, Lee YW, Kumar I, Ramazanov B, Zhang Y, Hernandez C, Lu AY, Neuenkirchen N, Deng J, Jin J, Kluger Y, Neubert TA, Bardwell VJ, Ivanova NB. A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs. Cell Stem Cell 2018, 22: 235-251.e9. PMID: 29337181, PMCID: PMC5797497, DOI: 10.1016/j.stem.2017.12.002.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationChromatinF-Box ProteinsHistonesHuman Embryonic Stem CellsHumansJumonji Domain-Containing Histone DemethylasesLysineMethylationMultiprotein ComplexesPolycomb Repressive Complex 1Polycomb Repressive Complex 2Promoter Regions, GeneticProtein DomainsProto-Oncogene ProteinsRepressor ProteinsConceptsEmbryonic stem cellsHuman embryonic stem cellsPolycomb domainsNon-canonical PRC1 complexesKey developmental lociNon-canonical complexesPolycomb group (PcG) proteinsE3 ubiquitin ligasesStem cell systemInitiation of differentiationDevelopmental lociPRC1 complexesRepressive chromatinRepressor functionPRC1.1 complexMesoderm lineageGroup proteinsCo-repressorAccessory subunitsDifferentiation programCanonical complexDevelopmental systemsC-terminusGene targetsN-terminus
2017
Post-transcriptional regulation of mouse neurogenesis by Pumilio proteins
Zhang M, Chen D, Xia J, Han W, Cui X, Neuenkirchen N, Hermes G, Sestan N, Lin H. Post-transcriptional regulation of mouse neurogenesis by Pumilio proteins. Genes & Development 2017, 31: 1354-1369. PMID: 28794184, PMCID: PMC5580656, DOI: 10.1101/gad.298752.117.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCytoplasmDentate GyrusFemaleFragile X Mental Retardation ProteinGene Expression Regulation, DevelopmentalGene Knockout TechniquesGene SilencingLearning DisabilitiesMaleMemory DisordersMiceNeural Stem CellsNeurogenesisNeuronsRNA, MessengerRNA-Binding ProteinsStem CellsConceptsPost-transcriptional regulationPost-transcriptional regulatorsNeural stem cellsTarget mRNAsMost target mRNAsRNA-dependent interactionCross-linking immunoprecipitationThousands of mRNAsMental retardation proteinPUM proteinsPumilio proteinsPumilio 1Mouse neurogenesisMammalian neurogenesisPerinatal apoptosisPUM1PUM2Stem cellsProteinCommon targetMRNARegulatorNeurogenesisCell compositionRegulation
2015
Reconstitution of the human U snRNP assembly machinery reveals stepwise Sm protein organization
Neuenkirchen N, Englbrecht C, Ohmer J, Ziegenhals T, Chari A, Fischer U. Reconstitution of the human U snRNP assembly machinery reveals stepwise Sm protein organization. The EMBO Journal 2015, 34: 1925-1941. PMID: 26069323, PMCID: PMC4547896, DOI: 10.15252/embj.201490350.Peer-Reviewed Original ResearchConceptsSMN complexAssembly machinerySm proteinsSpliceosomal U snRNPsDetailed molecular dissectionTrans-acting factorsSpontaneous conformational changesBiochemical reconstitutionPRMT5 complexU snRNPsProtein complexesMolecular dissectionProtein substratesProtein organizationIndividual proteinsConformational changesFaithful deliveryMode of actionRecombinant sourcesCoordinated actionBrownian machineMechanistic insightsSnRNPsProteinAssembly reactionReassessment of Piwi Binding to the Genome and Piwi Impact on RNA Polymerase II Distribution
Lin H, Chen M, Kundaje A, Valouev A, Yin H, Liu N, Neuenkirchen N, Zhong M, Snyder M. Reassessment of Piwi Binding to the Genome and Piwi Impact on RNA Polymerase II Distribution. Developmental Cell 2015, 32: 772-774. PMID: 25805139, PMCID: PMC4472434, DOI: 10.1016/j.devcel.2015.03.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsBase SequenceBinding SitesChromatin ImmunoprecipitationChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNA-Binding ProteinsDrosophila melanogasterDrosophila ProteinsGenomeHigh-Throughput Nucleotide SequencingHistone MethyltransferasesHistone-Lysine N-MethyltransferaseMethyltransferasesRNA InterferenceRNA Polymerase IIRNA, Small InterferingSequence Analysis, DNAConceptsRNA polymerase II distributionGenomic targetsHeterochromatin protein 1aRNA polymerase IICurrent bioinformatics methodsPiwi mutantsDrosophila PiwiPolymerase IIDevelopmental cellsPericentric regionsHistone methyltransferaseBioinformatics methodsBioinformatics pipelineProtein 1APiwiGenomePiRNAsEuchromatinMutantsMethyltransferaseSites