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 ResearchConceptsSingle 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
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 ResearchMeSH KeywordsAnimalsDNA, ComplementaryFemaleGene DeletionGene Expression RegulationMaleMiceMice, Inbred StrainsMice, KnockoutRNA, Long NoncodingTranscriptomeX Chromosome InactivationConceptsX-chromosome inactivationAutosomal gene regulationGene regulationDouble deletionOrgan-specific mannerChromosome inactivationGene setsX chromosomeTranscriptional effectsExpression signaturesLociCell linesDeletionGenesRegulationVivo contributionRecent evidenceMegadomainsAutosomesFIRREMutantsChromosomesMain driversBiologySuperloopsDifferential regulation of OCT4 targets facilitates reacquisition of pluripotency
Thakurela S, Sindhu C, Yurkovsky E, Riemenschneider C, Smith ZD, Nachman I, Meissner A. Differential regulation of OCT4 targets facilitates reacquisition of pluripotency. Nature Communications 2019, 10: 4444. PMID: 31570708, PMCID: PMC6768871, DOI: 10.1038/s41467-019-11741-5.Peer-Reviewed Original ResearchConceptsEctopic transcription factorsReacquisition of pluripotencySomatic cell reprogrammingCis-regulatory elementsTranscription factor expressionExact molecular mechanismsOCT4 targetsPluripotent stem cellsPluripotency inductionCell reprogrammingTranscription factorsSomatic cellsMolecular mechanismsDifferential regulationPluripotencyStem cellsVivo differentiationPrimary targetCellsFactor expressionFinal stepExperimental systemReprogrammingTargetDifferentiation
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 reductionImmunoprecipitationGenetic 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
2013
Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition
Zhang RR, Cui QY, Murai K, Lim YC, Smith ZD, Jin S, Ye P, Rosa L, Lee YK, Wu HP, Liu W, Xu ZM, Yang L, Ding YQ, Tang F, Meissner A, Ding C, Shi Y, Xu GL. Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition. Cell Stem Cell 2013, 13: 237-245. PMID: 23770080, PMCID: PMC4474382, DOI: 10.1016/j.stem.2013.05.006.Peer-Reviewed Original ResearchConceptsNeural progenitor cell proliferationProgenitor cell proliferationCohort of genesEmbryonic stem cellsCell proliferationNeural progenitor cellsAdult neural progenitor cellsTET dioxygenasesEpigenetic regulationAdult mouse brainBiological functionsHippocampal neurogenesisProgenitor proliferationTET1DNA hydroxylationStem cellsProgenitor cellsAdult hippocampal neurogenesisAdult brainProliferationMouse brainNeurogenesisImportant roleCellsDioxygenasesDNA methylation: roles in mammalian development
Smith ZD, Meissner A. DNA methylation: roles in mammalian development. Nature Reviews Genetics 2013, 14: 204-220. PMID: 23400093, DOI: 10.1038/nrg3354.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsDNA methylationMammalian developmentPaternal genomeEmbryonic lineagesEpigenetic mechanismsPrimordial germ cell specificationDNA methylation erasureDNA methylation functionsKey PointsDNA methylationGerm cell specificationGermline-specific genesGlobal nuclear organizationSimilar epigenetic mechanismsTranscription factor bindingStem cellsPre-implantation stagesAdult stem cellsCpG island methylationMethylation erasureHeritable memoryMethylation functionsCell specificationCpG densityLineage specification
2009
Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses
Amit I, Garber M, Chevrier N, Leite AP, Donner Y, Eisenhaure T, Guttman M, Grenier JK, Li W, Zuk O, Schubert LA, Birditt B, Shay T, Goren A, Zhang X, Smith Z, Deering R, McDonald RC, Cabili M, Bernstein BE, Rinn JL, Meissner A, Root DE, Hacohen N, Regev A. Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses. Science 2009, 326: 257-263. PMID: 19729616, PMCID: PMC2879337, DOI: 10.1126/science.1179050.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaChromatin Assembly and DisassemblyDendritic CellsDNA, Single-StrandedFeedback, PhysiologicalGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksInflammationLipopeptidesLipopolysaccharidesMiceMice, Inbred C57BLPoly I-CRNA-Binding ProteinsToll-Like ReceptorsTranscription FactorsTranscription, GeneticVirusesConceptsTranscriptional responseRegulatory networksMajor transcriptional responsePrimary mammalian cellsCellular transcriptional responsesPathogen-sensing pathwaysChromatin modifiersPathogen responseCandidate regulatorsCore regulatorsMammalian cellsTranscription factorsGenomic dataGene expressionRegulatory functionsUnbiased approachUnbiased strategyRegulatorUnbiased reconstructionPrimary dendritic cellsCellsRNAProteinPathwayPathogens