2024
X-linked deletion of Crossfirre, Firre, and Dxz4 in vivo uncovers diverse phenotypes and combinatorial effects on autosomes
Hasenbein T, Hoelzl S, Smith Z, Gerhardinger C, Gonner M, Aguilar-Pimentel A, Amarie O, Becker L, Calzada-Wack J, Dragano N, da Silva-Buttkus P, Garrett L, Hölter S, Kraiger M, Östereicher M, Rathkolb B, Sanz-Moreno A, Spielmann N, Wurst W, Gailus-Durner V, Fuchs H, Hrabě de Angelis M, Meissner A, Engelhardt S, Rinn J, Andergassen D. X-linked deletion of Crossfirre, Firre, and Dxz4 in vivo uncovers diverse phenotypes and combinatorial effects on autosomes. Nature Communications 2024, 15: 10631. PMID: 39638999, PMCID: PMC11621363, DOI: 10.1038/s41467-024-54673-5.Peer-Reviewed Original ResearchConceptsAutosomal gene regulationRegions genome-wideAllele-specific analysisSex-specific lociLoci in vivoX-linked genesRandom X-chromosome inactivationX-chromosome inactivationSex-specific phenotypesFirre locusGenome-wideIn vivo roleChromatin structureGene regulationX chromosomeEpigenetic featuresDXZ4Epigenetic profilesKnockout studiesLociDiverse phenotypesLncRNA FIRREFunctional roleCombinatorial effectsFIRRE
2020
TETs compete with DNMT3 activity in pluripotent cells at thousands of methylated somatic enhancers
Charlton J, Jung EJ, Mattei AL, Bailly N, Liao J, Martin EJ, Giesselmann P, Brändl B, Stamenova EK, Müller FJ, Kiskinis E, Gnirke A, Smith ZD, Meissner A. TETs compete with DNMT3 activity in pluripotent cells at thousands of methylated somatic enhancers. Nature Genetics 2020, 52: 819-827. PMID: 32514123, PMCID: PMC7415576, DOI: 10.1038/s41588-020-0639-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell LineDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEmbryonic Stem CellsEnhancer Elements, GeneticEpigenesis, GeneticGene Expression Regulation, DevelopmentalGerm LayersHumansMiceMice, KnockoutMixed Function OxygenasesPluripotent Stem CellsProto-Oncogene ProteinsConceptsPluripotent cellsHuman embryonic stem cell linesEmbryonic stem cell linesDNA methylation landscapeEpiblast stem cellsStem cell linesGlobal methylation levelsMethylation landscapeMouse ESCsMammalian cellsRegulatory sequencesDNA methylationSomatic tissuesNegative regulatorTET expressionMethylation levelsDynamic locusStem cellsCell linesLociDemethylationRegulatorEnhancerCellsTet
2019
In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation
Andergassen D, Smith ZD, Lewandowski JP, Gerhardinger C, Meissner A, Rinn JL. In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation. ELife 2019, 8: e47214. PMID: 31738164, PMCID: PMC6860989, DOI: 10.7554/elife.47214.Peer-Reviewed Original ResearchConceptsX-chromosome inactivationAutosomal gene regulationGene regulationDouble deletionOrgan-specific mannerChromosome inactivationGene setsX chromosomeTranscriptional effectsExpression signaturesLociCell linesDeletionGenesRegulationVivo contributionRecent evidenceMegadomainsAutosomesFIRREMutantsChromosomesMain driversBiologySuperloops
2018
Genetic determinants and epigenetic effects of pioneer-factor occupancy
Donaghey J, Thakurela S, Charlton J, Chen JS, Smith ZD, Gu H, Pop R, Clement K, Stamenova EK, Karnik R, Kelley DR, Gifford CA, Cacchiarelli D, Rinn JL, Gnirke A, Ziller MJ, Meissner A. Genetic determinants and epigenetic effects of pioneer-factor occupancy. Nature Genetics 2018, 50: 250-258. PMID: 29358654, PMCID: PMC6517675, DOI: 10.1038/s41588-017-0034-3.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsBinding SitesCell LineageCells, CulturedComputational BiologyDNAEpigenesis, GeneticEpistasis, GeneticGATA4 Transcription FactorGene Expression RegulationGene Regulatory NetworksGenes, SwitchHEK293 CellsHep G2 CellsHepatocyte Nuclear Factor 3-betaHumansOctamer Transcription Factor-3Protein BindingTranscription FactorsConceptsCell typesAlternative cell typesGenomic occupancyDNA accessibilityPioneer factorsDNA replicationDNA methylationDNA sequencesEpigenetic effectsGene expressionDevelopmental transitionsMolecular componentsGenetic determinantsFOXA2TF activityGATA4Specific bindingExpressionSubsequent lossOccupancyEnrichmentMethylationLociLow enrichmentBinding
2014
In Vivo and In Vitro Dynamics of Undifferentiated Embryonic Cell Transcription Factor 1
Galonska C, Smith ZD, Meissner A. In Vivo and In Vitro Dynamics of Undifferentiated Embryonic Cell Transcription Factor 1. Stem Cell Reports 2014, 2: 245-252. PMID: 24672748, PMCID: PMC3964277, DOI: 10.1016/j.stemcr.2014.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCell DifferentiationCell LineCellular ReprogrammingChromosomal Proteins, Non-HistoneDNAEmbryo, MammalianEmbryonic Stem CellsGene ExpressionGene Expression Regulation, DevelopmentalGene OrderGenes, ReporterGenetic VectorsMicePluripotent Stem CellsProtein BindingTrans-ActivatorsTranscription FactorsConceptsEmbryonic cell transcription factor 1Transcription factor 1Reporter linesDiverse rolesUndifferentiated embryonic cell transcription factor 1Factor 1Stem cell conditionsPluripotent stem cellsTargeted locusTranscription factorsDynamic regulationGerm layersBiotinylation systemUTF1Stem cellsCell conditionsPluripotencyGermlineLociRegulatorReporterBetter understandingRegulationLinesMajor interest
2011
Lung Stem Cell Self-Renewal Relies on BMI1-Dependent Control of Expression at Imprinted Loci
Zacharek SJ, Fillmore CM, Lau AN, Gludish DW, Chou A, Ho JW, Zamponi R, Gazit R, Bock C, Jäger N, Smith ZD, Kim TM, Saunders AH, Wong J, Lee JH, Roach RR, Rossi DJ, Meissner A, Gimelbrant AA, Park PJ, Kim CF. Lung Stem Cell Self-Renewal Relies on BMI1-Dependent Control of Expression at Imprinted Loci. Cell Stem Cell 2011, 9: 272-281. PMID: 21885022, PMCID: PMC3167236, DOI: 10.1016/j.stem.2011.07.007.Peer-Reviewed Original ResearchMeSH KeywordsAdult Stem CellsAnimalsCell SurvivalCells, CulturedCyclin-Dependent Kinase Inhibitor p16Gene Expression ProfilingGene Expression Regulation, DevelopmentalGenes, p16Genetic LociGenomic ImprintingLungMiceMice, Mutant StrainsNuclear ProteinsPolycomb Repressive Complex 1Proto-Oncogene ProteinsRegenerationRepressor ProteinsRNA, Small InterferingS-Phase Kinase-Associated ProteinsConceptsImprinted lociBronchioalveolar stem cellsStem cellsAdult tissue-specific stem cellsTissue-specific stem cellsLung epithelial stem cellsSelf-renewal defectLung epithelial cell injuryLung stem cellsDevelopmental processesEpithelial stem cellsExpression of p57Bmi1 knockout miceLung cellsGenesAdult cellsLociExpressionCellsAllelesRegulationKnockout miceEpithelial cell injuryFundamental questionsCDKN1CReprogramming Factor Expression Initiates Widespread Targeted Chromatin Remodeling
Koche RP, Smith ZD, Adli M, Gu H, Ku M, Gnirke A, Bernstein BE, Meissner A. Reprogramming Factor Expression Initiates Widespread Targeted Chromatin Remodeling. Cell Stem Cell 2011, 8: 96-105. PMID: 21211784, PMCID: PMC3220622, DOI: 10.1016/j.stem.2010.12.001.Peer-Reviewed Original ResearchConceptsPluripotent stem cell stateEuchromatic histone modificationsRepressive H3K27me3 modificationGenome-wide changesStem cell stateChromatin remodelingH3K4 methylationHistone modificationsH3K27me3 modificationEpigenetic responsesTranscriptional changesSomatic cellsRegulatory eventsGene promoterEpigenetic changesCell statesCorresponding lociSomatic identityMechanistic questionsFactor inductionEarly eventsLociH3K4me2ReprogrammingRapid progress