2022
Precision 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
2024
Piwi regulates the usage of alternative transcription start sites in the Drosophila ovary
Chen J, Liu N, Qi H, Neuenkirchen N, Huang Y, Lin H. Piwi regulates the usage of alternative transcription start sites in the Drosophila ovary. Nucleic Acids Research 2024, 53: gkae1160. PMID: 39657757, PMCID: PMC11724274, DOI: 10.1093/nar/gkae1160.Peer-Reviewed Original ResearchTranscription start siteTranscription start site usageFacilitates chromatin transcriptionDrosophila ovaryOvarian somatic cellsStart siteCap analysis of gene expression sequencingAlternative transcription start sitesSomatic cellsPol II initiationRNA polymerase IIAlternative transcription initiationRNA-binding proteinsCultured ovarian somatic cellsGene expression sequencingMRNA elongationPolymerase IIPol IITranscription initiationChromatin transcriptionTranscriptional regulationExpressed sequencesMutant ovariesPIWICap analysisTranscription 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
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 genesEmbryogenesisGenesTranscriptsSplicingOogenesisTranscriptionOrganogenesisRegulationRoleProductionNeurogenesisDivisionDevelopmentTranslation
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
Reassessment 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
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