2021
Smart-RRBS for single-cell methylome and transcriptome analysis
Gu H, Raman AT, Wang X, Gaiti F, Chaligne R, Mohammad AW, Arczewska A, Smith ZD, Landau DA, Aryee MJ, Meissner A, Gnirke A. Smart-RRBS for single-cell methylome and transcriptome analysis. Nature Protocols 2021, 16: 4004-4030. PMID: 34244697, PMCID: PMC8672372, DOI: 10.1038/s41596-021-00571-9.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnti-Bacterial AgentsDNADNA (Cytosine-5-)-MethyltransferasesDoxycyclineEpigenomeGene Expression RegulationHumansIntracellular Signaling Peptides and ProteinsRNA, MessengerSingle-Cell AnalysisTranscriptomeConceptsSingle cellsProtein-coding genesSingle-cell methylomesSame single cellMulti-omics approachRare cell populationsSmart-seq2Transcriptional statesDNA methylomeTranscriptome analysisImportant mechanistic insightsEpigenetic modificationsDNA methylationDissected tissue samplesGenomic DNAHundreds of cellsCellular heterogeneityFlow sortingRegulatory consequencesMethylomeEpigenetic promoterMechanistic insightsCell populationsCellsTypical single cell
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
Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression
Tsankov AM, Wadsworth MH, Akopian V, Charlton J, Allon SJ, Arczewska A, Mead BE, Drake RS, Smith ZD, Mikkelsen TS, Shalek AK, Meissner A. Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression. Development 2019, 146: dev174722. PMID: 31515224, PMCID: PMC6803377, DOI: 10.1242/dev.174722.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell DifferentiationDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEnhancer Elements, GeneticEntropyGene Expression Regulation, DevelopmentalHuman Embryonic Stem CellsHumansMaleRepressor ProteinsRNA, MessengerTranscription, GeneticConceptsGlobal methylation levelsTranscriptional repressionSingle-cell RNA-sequencing dataMethylation levelsNew cell fatesMaintenance of pluripotencyHuman embryonic stem cellsMethylation of cytosineRNA-sequencing dataCell-cell variabilityStem cellsEmbryonic stem cellsHuman pluripotent stem cellsDNA methyltransferase activityMRNA expression dataPluripotent stem cellsTranscriptional variabilityMethyltransferases Dnmt3aCell fateEpigenetic regulatorsMethyltransferase DNMT3AExtrinsic signalsHigh-resolution viewMethyltransferase activityProper differentiation
2018
Targets and genomic constraints of ectopic Dnmt3b expression
Zhang Y, Charlton J, Karnik R, Beerman I, Smith ZD, Gu H, Boyle P, Mi X, Clement K, Pop R, Gnirke A, Rossi DJ, Meissner A. Targets and genomic constraints of ectopic Dnmt3b expression. ELife 2018, 7: e40757. PMID: 30468428, PMCID: PMC6251628, DOI: 10.7554/elife.40757.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationEmbryonic Stem CellsGene ExpressionGene Expression RegulationHumansMice, TransgenicNeoplasmsRecombinant ProteinsConceptsDNA methylationCpG islandsDe novo DNA methyltransferase DNMT3BCertain CpG islandsDNA methyltransferase DNMT3BGenome-wide dataCpG island hypermethylationDifferent cell typesMammalian genomesChromatin landscapeGenomic constraintsTranscriptional statesCancer methylomeMethyltransferase DNMT3BBisulfite sequencingGenomic targetsIsland hypermethylationResponsible enzymeDNMT3B expressionAberrant methylationDNMT3BMethylationCell typesH3K27me3Essential roleGlobal delay in nascent strand DNA methylation
Charlton J, Downing TL, Smith ZD, Gu H, Clement K, Pop R, Akopian V, Klages S, Santos DP, Tsankov AM, Timmermann B, Ziller MJ, Kiskinis E, Gnirke A, Meissner A. Global delay in nascent strand DNA methylation. Nature Structural & Molecular Biology 2018, 25: 327-332. PMID: 29531288, PMCID: PMC5889353, DOI: 10.1038/s41594-018-0046-4.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell ProliferationCpG IslandsCytosineDNADNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA ReplicationEmbryonic Stem CellsEpigenesis, GeneticGene Expression RegulationGenome, HumanHCT116 CellsHumansMaleMethylationMitosisMotor NeuronsNeoplasmsSequence Analysis, RNATranscription FactorsConceptsCytosine methylationCpG methylationGenome-wide bisulfite sequencingCis-regulatory elementsEmbryonic stem cellsCancer cell line HCT116Cell cycle arrestEpigenetic informationMammalian developmentGene regulationMitotic transmissionEpigenetic heterogeneityEpigenetic roleBisulfite sequencingCell line HCT116DNA methylationHuman cellsMethylationHeterogeneous methylationStem cellsCellsBrdU labelingPronounced lagGlobal reductionImmunoprecipitation