2021
The Essential Function of SETDB1 in Homologous Chromosome Pairing and Synapsis during Meiosis
Cheng EC, Hsieh CL, Liu N, Wang J, Zhong M, Chen T, Li E, Lin H. The Essential Function of SETDB1 in Homologous Chromosome Pairing and Synapsis during Meiosis. Cell Reports 2021, 34: 108575. PMID: 33406415, PMCID: PMC8513770, DOI: 10.1016/j.celrep.2020.108575.Peer-Reviewed Original ResearchConceptsEarly meiosisEarly meiotic prophase IFunction of SETDB1Homologous chromosome pairingMeiotic prophase IHistone-lysine N-methyltransferaseMeiotic silencingSurvival of spermatocytesGermline developmentBouquet formationHomologous chromosomesLineage genesChromosome pairingBivalent formationPericentromeric regionProphase IApoptosis of spermatocytesSETDB1Essential functionsHomologous bivalentsH3K9me3Meiotic arrestMeiosisSpermatocytesN-methyltransferase
2020
PIWIL1 promotes gastric cancer via a piRNA-independent mechanism
Shi S, Yang ZZ, Liu S, Yang F, Lin H. PIWIL1 promotes gastric cancer via a piRNA-independent mechanism. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 22390-22401. PMID: 32848063, PMCID: PMC7486755, DOI: 10.1073/pnas.2008724117.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsPIWI proteinsGastric cancer cellsNonsense-mediated mRNA decay mechanismPiRNA-independent mechanismDomain protein familyMRNA decay mechanismMammalian somatic tissuesRNA deep sequencingGastric cancer cell line SNU-1Cancer cellsGastric cancer cell proliferationRNA pathwaysPPD proteinsProtein familyPiwil1 geneSomatic tissuesSomatic cancersCancer cell proliferationDeep sequencingRegulatory mechanismsOncogenic functionPIWIL1Gastric cancer tissuesDetectable function
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 genesEmbryogenesisGenesTranscriptsSplicingOogenesisTranscriptionOrganogenesisRegulationRoleProductionNeurogenesisDivisionDevelopmentTranslationMIWI2 targets RNAs transcribed from piRNA‐dependent regions to drive DNA methylation in mouse prospermatogonia
Watanabe T, Cui X, Yuan Z, Qi H, Lin H. MIWI2 targets RNAs transcribed from piRNA‐dependent regions to drive DNA methylation in mouse prospermatogonia. The EMBO Journal 2018, 37 PMID: 30108053, PMCID: PMC6138435, DOI: 10.15252/embj.201695329.Peer-Reviewed Original ResearchConceptsDNA methylationRetrotransposon sequencesSmall RNAsArgonaute/Piwi proteinsPiwi protein MIWI2Suppressive epigenetic marksMouse prospermatogoniaChromatin statePIWI proteinsUnderlying molecular mechanismsDiverse organismsEpigenetic marksPiRNA clustersNascent RNAEpigenetic regulationTranslational regulationMIWI2RNA degradationRepeat sequencesGene expressionMolecular mechanismsTarget RNAMethylationRNAPiRNAsA critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila
Parikh RY, Lin H, Gangaraju VK. A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila. Journal Of Biological Chemistry 2018, 293: 9140-9147. PMID: 29735528, PMCID: PMC6005430, DOI: 10.1074/jbc.ac118.003264.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsArgonaute ProteinsDNA Transposable ElementsDrosophilaDrosophila ProteinsFemaleGene Expression RegulationGene SilencingGenomic InstabilityGerm CellsMaleMolecular ChaperonesNuclear Pore Complex ProteinsProtein Interaction MapsRNA, Small InterferingTranscription, GeneticConceptsPIWI-interacting RNAsPing-pong cycleNuclear pore complexPiRNA biogenesisGermline knockdownPiRNA pathwayAntisense Piwi-interacting RNAsPiRNA precursor transcriptionSmall noncoding RNAsPiwi functionSilence transposonsPIWI proteinsShort hairpin RNACritical roleArgonaute 3Pore complexNoncoding RNAsGenomic instabilityNuclear localizationGene expressionTransposonNup358Germ cellsBiogenesisHairpin RNANovel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer
Weng W, Liu N, Toiyama Y, Kusunoki M, Nagasaka T, Fujiwara T, Wei Q, Qin H, Lin H, Ma Y, Goel A. Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer. Molecular Cancer 2018, 17: 16. PMID: 29382334, PMCID: PMC5791351, DOI: 10.1186/s12943-018-0767-3.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overApoptosisBiomarkers, TumorCell DeathCell ProliferationColorectal NeoplasmsDisease ProgressionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingOncogenesPrognosisRNA InterferenceRNA, Small InterferingConceptsPIWI-interacting RNAsSmall RNA sequencingGene expression profiling resultsImportant epigenetic regulatorsDownstream target genesExpression profiling resultsCell survival pathwaysColorectal cancerPotential prognostic biomarkerTumor suppressor genePrognostic biomarkerEpigenetic regulatorsSequence complementarityNoncoding RNAsRNA sequencingTarget genesExpression profilingBiological functionsGene expressionSurvival pathwaysSuppressor geneClinical significanceDirect targetNovel oncogeneOncogenic mediators
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
2016
Tudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila
Ku HY, Gangaraju VK, Qi H, Liu N, Lin H. Tudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila. PLOS Genetics 2016, 12: e1005813. PMID: 26808625, PMCID: PMC4726654, DOI: 10.1371/journal.pgen.1005813.Peer-Reviewed Original ResearchConceptsPiRNA biogenesisPrimordial germ cellsPiwi expressionTudor-SNSomatic cellsGerm cellsDiverse molecular functionsPost-transcriptional regulationEmbryonic somatic cellsPiwi mutantsDosage-dependent mannerGermline developmentPIWI proteinsMutant phenotypeMeiotic cytokinesisMolecular functionsSpliceosome assemblyPiwiEpigenetic programmingDiverse functionsBiological functionsAdult ovariesBiogenesisTransposonMale fertility
2015
Poreless eggshells
Lin H, Matzuk MM. Poreless eggshells. Journal Of Clinical Investigation 2015, 125: 4005-4007. PMID: 26485282, PMCID: PMC4639988, DOI: 10.1172/jci84692.Peer-Reviewed Original ResearchConceptsNuclear pore complex functionMissense mutationsSpecific amino acid changesAmino acid changesRecessive missense mutationSomatic cellsNucleoporin 107Human mutationsGenetic materialAcid changesExtragonadal functionsOvarian developmentOocyte developmentMutationsGenesSole sourceFemale genetic materialIntrinsic factorsComplex functionsOrthologsAbnormal ovarian developmentFollicular developmentEmbryosFliesOocytesPiwi Is a Key Regulator of Both Somatic and Germline Stem Cells in the Drosophila Testis
Gonzalez J, Qi H, Liu N, Lin H. Piwi Is a Key Regulator of Both Somatic and Germline Stem Cells in the Drosophila Testis. Cell Reports 2015, 12: 150-161. PMID: 26119740, PMCID: PMC4497877, DOI: 10.1016/j.celrep.2015.06.004.Peer-Reviewed Original ResearchConceptsGermline stem cellsDrosophila testisSomatic cyst cellsPIWI-piRNA pathwayStem cell maintenanceCell-autonomous functionStem cellsGerm cell differentiationStem cell typesFasciclin 3GSC daughtersGermline functionSomatic rolePiwi expressionCyst cellsCell maintenanceEpigenetic mechanismsPiwiGenes keyNuclear localizationKey regulatorMolecular mechanismsCell differentiationGonadal developmentCell types
2014
Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline
Watanabe T, Cheng EC, Zhong M, Lin H. Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline. Genome Research 2014, 25: 368-380. PMID: 25480952, PMCID: PMC4352877, DOI: 10.1101/gr.180802.114.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsPiRNA pathwayRetrotransposon sequencesIntergenic regionMammalian PIWI-interacting RNAsRNA regulatory networkLate spermatocytesVivo functional analysisDegradation of mRNAUTR of mRNAsSlicer activityEukaryotic genomesLncRNA transcriptomeRegulatory networksRegulatory sequencesRepetitive sequencesPseudogenesMRNA stabilityFunctional analysisLncRNAsWidespread expressionSpermatid stageRetrotransposonsMRNATransposonGeneration of transgenic Hydra by embryo microinjection.
Juliano CE, Lin H, Steele RE. Generation of transgenic Hydra by embryo microinjection. Journal Of Visualized Experiments 2014, 51888. PMID: 25285460, PMCID: PMC4828061, DOI: 10.3791/51888.Peer-Reviewed Original ResearchConceptsTransgenic HydraFundamental biological processesEarly stage embryosPatches of tissuePure cell populationsMulticellular animalsStudy of regenerationGene functionMolecular functionsPhylum CnidariaParticular lineageTransgenic linesGene perturbationsSister groupTransgenic tissuesTransgenic methodsPromoter functionAsexual propagationBiological processesEmbryo microinjectionStage embryosLive cellsStem cellsHatchlingsBiochemical analysis
2013
Piwi Genes Are Dispensable for Normal Hematopoiesis in Mice
Nolde MJ, Cheng EC, Guo S, Lin H. Piwi Genes Are Dispensable for Normal Hematopoiesis in Mice. PLOS ONE 2013, 8: e71950. PMID: 24058407, PMCID: PMC3751959, DOI: 10.1371/journal.pone.0071950.Peer-Reviewed Original ResearchConceptsPiwi genesHematopoietic stem cellsNormal adult hematopoiesisPIWI protein familyStem cellsStem/progenitor cellsDiverse organismsAdult hematopoiesisProtein familyLong-term hematopoiesisMyeloablative stressCompetitive transplantationTransient expressionHuman leukemia cell linesHSC compartmentLeukemia cell linesGenesProliferative stateNormal hematopoiesisCell typesMIWI2Progenitor cellsLineage reconstitutionHematopoiesisCell proliferationTdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline
Saxe JP, Chen M, Zhao H, Lin H. Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline. The EMBO Journal 2013, 32: 1869-1885. PMID: 23714778, PMCID: PMC3981179, DOI: 10.1038/emboj.2013.121.Peer-Reviewed Original ResearchConceptsPrimary piRNA biogenesisPiRNA biogenesisKH domain-containing proteinPiRNA biogenesis pathwayPing-pong cycleDomain-containing proteinsMature piRNAsPIWI proteinsBiogenesis pathwayMitochondrial proteinsEpigenetic programmingNuclear localizationCytoplasmic localizationZygotene stageBiogenesisTDRKHArginine residuesMeiotic arrestMIWI2MIWIDistinct populationsProteinMutantsGermlineRNAFunction of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity
Darricarrère N, Liu N, Watanabe T, Lin H. Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 1297-1302. PMID: 23297219, PMCID: PMC3557079, DOI: 10.1073/pnas.1213283110.Peer-Reviewed Original ResearchConceptsPIWI proteinsPiRNA biogenesisSlicer activityPIWI-interacting RNA (piRNA) biogenesisEndonuclease activityFunction of PiwiNuclear Piwi proteinSecondary piRNA biogenesisGerm line developmentPiwi functionPiwi membersArgonaute proteinsRNA biogenesisArgonaute 3Transgenic fliesPiwiSomatic cellsCatalytic triadEpigenetic factorsRegulatory functionsBiogenesisOnly memberProteinTransposonRecent evidence
2012
piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism
Beyret E, Liu N, Lin H. piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism. Cell Research 2012, 22: 1429-1439. PMID: 22907665, PMCID: PMC3463270, DOI: 10.1038/cr.2012.120.Peer-Reviewed Original ResearchConceptsPIWI proteinsPing-pong mechanismSmall non-coding RNAsSame DNA strandNon-coding RNAsPiRNA biogenesisGermline developmentDiverse organismsEpigenetic regulationPiRNAsMIWIRepeat sequencesMILISame locusSequence featuresNucleotide positionsPostnatal testisBroad functionsAdult testisMouse testisDNA strandsAdult spermatogenesisProteinBiogenesisPrimary pathwayEssential Roles of the Chromatin Remodeling Factor Brg1 in Spermatogenesis in Mice1
Wang J, Gu H, Lin H, Chi T. Essential Roles of the Chromatin Remodeling Factor Brg1 in Spermatogenesis in Mice1. Biology Of Reproduction 2012, 86: 186, 1-10. PMID: 22495890, PMCID: PMC3386149, DOI: 10.1095/biolreprod.111.097097.Peer-Reviewed Original ResearchConceptsMeiotic recombinationSomatic cellsDNA repairMeiotic sex chromosome inactivationChromatin Remodeling Factor BRG1Sex chromosome inactivationChromatin-remodeling complexBAF chromatin-remodeling complexImpaired homologous recombinationEssential roleRole of BRG1Chromatin regulationChromatin structureFactor BRG1Male germlineMammalian spermatogenesisSpatiotemporal regulationChromosome inactivationCatalytic subunitHomologous recombinationMidpachytene stageBRG1Expression patternsGene expressionGerm cellsPumilio 1 Suppresses Multiple Activators of p53 to Safeguard Spermatogenesis
Chen D, Zheng W, Lin A, Uyhazi K, Zhao H, Lin H. Pumilio 1 Suppresses Multiple Activators of p53 to Safeguard Spermatogenesis. Current Biology 2012, 22: 420-425. PMID: 22342750, PMCID: PMC3449084, DOI: 10.1016/j.cub.2012.01.039.Peer-Reviewed Original Research
2011
Small Noncoding RNAs in the Germline
Saxe JP, Lin H. Small Noncoding RNAs in the Germline. Cold Spring Harbor Perspectives In Biology 2011, 3: a002717. PMID: 21669983, PMCID: PMC3181032, DOI: 10.1101/cshperspect.a002717.Peer-Reviewed Original ResearchConceptsRNA pathwaysSmall noncoding RNAsTarget mRNAsNoncoding RNAsSmall RNA pathwaysPiRNA pathwayGermline specificationMicroRNA pathwayMiRNA pathwayGene regulationMRNA translationSomatic tissuesEpigenetic programmingDiverse functionsGene expressionRegulatory functionsGermlinePotent regulatorPathwayRNAMRNARegulationPiwiBiogenesisTransposonRole for piRNAs and Noncoding RNA in de Novo DNA Methylation of the Imprinted Mouse Rasgrf1 Locus
Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, Iida N, Hoki Y, Murphy PJ, Toyoda A, Gotoh K, Hiura H, Arima T, Fujiyama A, Sado T, Shibata T, Nakano T, Lin H, Ichiyanagi K, Soloway PD, Sasaki H. Role for piRNAs and Noncoding RNA in de Novo DNA Methylation of the Imprinted Mouse Rasgrf1 Locus. Science 2011, 332: 848-852. PMID: 21566194, PMCID: PMC3368507, DOI: 10.1126/science.1203919.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsDNA MethylationGenomic ImprintingMaleMiceMice, Inbred C57BLMitochondrial ProteinsModels, GeneticMutationPhospholipase DProteinsRas-GRF1Repetitive Sequences, Nucleic AcidRetroelementsRNA, Small InterferingRNA, UntranslatedSpermatogoniaTestisTranscription, GeneticConceptsRasgrf1 locusDNA methylationPIWI-interacting RNA (piRNA) pathwayDe novo DNA methylationMonoallelic gene expressionNovo DNA methylationParental germ lineDe novo methylationSequence-specific methylationDifferential DNA methylationRNA pathwaysGenomic imprintingNovo methylationRetrotransposon sequencesGerm lineNoncoding RNAsGene expressionDirect repeatsPiRNAsTarget RNADifferent lociMethylationLociRNASpecific sequences