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 ResearchConceptsDNA 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
2014
DNA methylation dynamics of the human preimplantation embryo
Smith ZD, Chan MM, Humm KC, Karnik R, Mekhoubad S, Regev A, Eggan K, Meissner A. DNA methylation dynamics of the human preimplantation embryo. Nature 2014, 511: 611-615. PMID: 25079558, PMCID: PMC4178976, DOI: 10.1038/nature13581.Peer-Reviewed Original ResearchConceptsGenome-scale DNA methylationMaternal-specific methylationDNA methylation dynamicsTransposable element activityEmbryonic stem cell derivationStem cell derivationEarly human embryogenesisHuman preimplantation embryosMethylation dynamicsDNA methylationHuman embryogenesisElement activityPreimplantation embryosCell derivationUnique modeMethylationEmbryogenesisMouse modelEmbryosRegulationExpression
2013
Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging
Beerman I, Bock C, Garrison BS, Smith ZD, Gu H, Meissner A, Rossi DJ. Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging. Cell Stem Cell 2013, 12: 413-425. PMID: 23415915, DOI: 10.1016/j.stem.2013.01.017.Peer-Reviewed Original ResearchConceptsDNA methylationHSC declineHematopoietic stem cell agingPolycomb repressive complex 2DNA methylation landscapeStem cell agingStem cell declineRepressive complex 2Global DNA methylationSite-specific alterationsHematopoietic lineage potentialMethylation landscapeDNA methylomeGenomic regionsLineage potentialEpigenomic alterationsDNA hypermethylationReplicative limitCell agingDownstream progenitorsFunctional analysisFunctional potentialMethylationProliferation of HSCsGenes
2012
A unique regulatory phase of DNA methylation in the early mammalian embryo
Smith ZD, Chan MM, Mikkelsen TS, Gu H, Gnirke A, Regev A, Meissner A. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 2012, 484: 339-344. PMID: 22456710, PMCID: PMC3331945, DOI: 10.1038/nature10960.Peer-Reviewed Original ResearchConceptsDNA methylationGenome-scale DNA methylation mapsLong terminal repeat (LTR) retroelementsDNA methylation mapsBase-resolution mapsEarly mammalian embryoCpG island promotersBlastocyst stageMammalian embryogenesisMethylation mapsPaternal genomeMammalian embryosEpigenetic modificationsEarly embryosSomatic cellsGlobal hypomethylationSomatic patternMouse gametesElement 1MethylationEmbryosMethylation valuesRegulatory phaseGametesZygotesGel-free multiplexed reduced representation bisulfite sequencing for large-scale DNA methylation profiling
Boyle P, Clement K, Gu H, Smith ZD, Ziller M, Fostel JL, Holmes L, Meldrim J, Kelley F, Gnirke A, Meissner A. Gel-free multiplexed reduced representation bisulfite sequencing for large-scale DNA methylation profiling. Genome Biology 2012, 13: r92. PMID: 23034176, PMCID: PMC3491420, DOI: 10.1186/gb-2012-13-10-r92.Peer-Reviewed Original Research
2010
Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution
Gu H, Bock C, Mikkelsen TS, Jäger N, Smith ZD, Tomazou E, Gnirke A, Lander ES, Meissner A. Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution. Nature Methods 2010, 7: 133-136. PMID: 20062050, PMCID: PMC2860480, DOI: 10.1038/nmeth.1414.Peer-Reviewed Original Research
2009
High-throughput bisulfite sequencing in mammalian genomes
Smith ZD, Gu H, Bock C, Gnirke A, Meissner A. High-throughput bisulfite sequencing in mammalian genomes. Methods 2009, 48: 226-232. PMID: 19442738, PMCID: PMC2864123, DOI: 10.1016/j.ymeth.2009.05.003.Peer-Reviewed Original ResearchConceptsDNA methylationHigh-throughput bisulfite sequencingCritical epigenetic markCpG-dense regionsGenome-wide distributionArray-based technologiesMammalian genomesEpigenetic marksMammalian developmentGenomic regionsRRBS librariesBisulfite sequencingMethylome profilingSequencing librariesRRBS librarySequence analysisMethylationRestriction digestionSequencingGenomeLibraryRelative coverageMspIProfilingSample throughput