2024
CpG island turnover events predict evolutionary changes in enhancer activity
Kocher A, Dutrow E, Uebbing S, Yim K, Rosales Larios M, Baumgartner M, Nottoli T, Noonan J. CpG island turnover events predict evolutionary changes in enhancer activity. Genome Biology 2024, 25: 156. PMID: 38872220, PMCID: PMC11170920, DOI: 10.1186/s13059-024-03300-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCpG IslandsEnhancer Elements, GeneticEvolution, MolecularHistone CodeHumansMiceSpecies SpecificityConceptsHuman-gained enhancersCpG islandsFunction of transcriptional enhancersEvolution of biological diversityHuman CpG islandsGene regulatory changesInfluence enhancer activityCpG island contentHistone modification levelsEnhanced activitySpecies-specific activityTrait evolutionNucleotide substitutionsHistone modificationsTranscriptional enhancersMouse orthologEvolutionary changesTurnover eventsModification levelsMammalian speciesMultiple tissuesEmbryonic developmentMouse diencephalonHuman embryonic developmentSpecies
2022
Modeling uniquely human gene regulatory function via targeted humanization of the mouse genome
Dutrow EV, Emera D, Yim K, Uebbing S, Kocher AA, Krenzer M, Nottoli T, Burkhardt DB, Krishnaswamy S, Louvi A, Noonan JP. Modeling uniquely human gene regulatory function via targeted humanization of the mouse genome. Nature Communications 2022, 13: 304. PMID: 35027568, PMCID: PMC8758698, DOI: 10.1038/s41467-021-27899-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell DifferentiationChondrocytesChondrogenesisEmbryo, MammalianEnhancer Elements, GeneticEpigenesis, GeneticExtremitiesGene Expression ProfilingGene Expression RegulationGene Knock-In TechniquesGenomeHomeodomain ProteinsHomozygoteHumansMesodermMice, Inbred C57BLModels, GeneticPan troglodytesPromoter Regions, GeneticTime FactorsConceptsHuman Accelerated RegionsGene expressionHuman-specific sequence changesDevelopmental gene regulationSingle-cell RNA sequencingGene regulatory functionsHuman evolutionEndogenous gene expressionAlters gene expressionSkeletal patterningMolecular functionsGene regulationChondrogenic mesenchymeMouse genomeRegulatory modificationHomozygous embryosLimb developmentTranscriptional enhancersTranscription factorsRNA sequencingEnhancer activityMouse embryosRegulatory functionsAccelerated regionSequence changes
2020
Massively parallel discovery of human-specific substitutions that alter enhancer activity
Uebbing S, Gockley J, Reilly SK, Kocher AA, Geller E, Gandotra N, Scharfe C, Cotney J, Noonan JP. Massively parallel discovery of human-specific substitutions that alter enhancer activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2007049118. PMID: 33372131, PMCID: PMC7812811, DOI: 10.1073/pnas.2007049118.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological EvolutionEnhancer Elements, GeneticGenome, HumanHumansNeocortexNeural Stem CellsPan troglodytesTranscription FactorsConceptsHuman-specific substitutionsHuman-gained enhancersGenetic changesEnhancer functionEnhancer activityHuman-specific genetic changesHuman evolutionGene regulatory elementsBackground genetic variationAncestral functionRegulatory evolutionEnhancer assaysGenetic variationRegulatory elementsNeural stem cellsHuman traitsNovel activityNonadditive wayRegulatory activityStem cellsFunctional impactDifferential activityParallel discoveryEnhancerEvolution
2016
Origin and evolution of developmental enhancers in the mammalian neocortex
Emera D, Yin J, Reilly SK, Gockley J, Noonan JP. Origin and evolution of developmental enhancers in the mammalian neocortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e2617-e2626. PMID: 27114548, PMCID: PMC4868431, DOI: 10.1073/pnas.1603718113.Peer-Reviewed Original ResearchConceptsRegulatory elementsDe novo birthMammalian stem lineageNovel regulatory sequencesWeak evolutionary constraintsMammalian neocortexBackground genomic sequencesDevelopmental enhancersEvolutionary constraintsMorphological innovationsStem lineageEutherian mammalsGenomic sequencesRegulatory sequencesPhylogenetic originComplex enhancerCell signalingGenomic backgroundMouse corticogenesisCell migrationMammalsMammalian forebrainEnhancerGenesLife cycle
2015
Evolutionary changes in promoter and enhancer activity during human corticogenesis
Reilly SK, Yin J, Ayoub AE, Emera D, Leng J, Cotney J, Sarro R, Rakic P, Noonan JP. Evolutionary changes in promoter and enhancer activity during human corticogenesis. Science 2015, 347: 1155-1159. PMID: 25745175, PMCID: PMC4426903, DOI: 10.1126/science.1260943.Peer-Reviewed Original ResearchConceptsCorrelated gene expression patternsSimilar transcription factorsGene expression patternsCommon regulatory mechanismHuman cortical evolutionPotential regulatory changesEvolutionary changeEpigenetic profilingEvolutionary expansionTranscription factorsGenetic mechanismsSite enrichmentEnhancer activityDevelopmental processesExpression patternsHuman corticogenesisRegulatory mechanismsMouse corticogenesisHuman higher cognitionCortical evolutionPromoterCorticogenesisCoordinated patternNeuronal proliferationEnhancer
2013
The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb
Cotney J, Leng J, Yin J, Reilly SK, DeMare LE, Emera D, Ayoub AE, Rakic P, Noonan JP. The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb. Cell 2013, 154: 185-196. PMID: 23827682, PMCID: PMC3785101, DOI: 10.1016/j.cell.2013.05.056.Peer-Reviewed Original ResearchConceptsCis-regulatory evolutionHistone modification H3K27acGenome-wide viewMouse limb developmentRegulatory activityGain of activityMost enhancersGene regulationEmbryonic limbLimb developmentHuman lineageEnhancer activityHuman embryonic tissuesGene expressionEmbryonic tissuesRegulatory functionsPromoterH3K27acMolecular driversGenetic causeHeterogeneous genetic causesEnhancerQuantitative readoutMorphological evolutionAnatomical featuresThe genomic landscape of cohesin-associated chromatin interactions
DeMare LE, Leng J, Cotney J, Reilly SK, Yin J, Sarro R, Noonan JP. The genomic landscape of cohesin-associated chromatin interactions. Genome Research 2013, 23: 1224-1234. PMID: 23704192, PMCID: PMC3730097, DOI: 10.1101/gr.156570.113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCCCTC-Binding FactorCell Cycle ProteinsChromatinChromatin ImmunoprecipitationChromosomal Proteins, Non-HistoneEnhancer Elements, GeneticGene Expression Regulation, DevelopmentalGenomeHistonesLimb BudsMiceMice, Inbred C57BLOrgan SpecificityPromoter Regions, GeneticProtein SubunitsRepressor ProteinsConceptsPaired-end tag sequencingGenome-wide scaleInsulator protein CTCFChromatin interaction analysisEnhancer-promoter interactionsEnhancer-promoter communicationEmbryonic stem cellsChromatin stateProtein CTCFChromatin interactionsTag sequencingDNA loopsRegulatory architectureMouse limbRegulatory outputMouse embryosGenomic landscapeMultiple tissuesCohesinStem cellsCTCFPromoterDemarcate regionsInteraction analysisGenome
2012
Chromatin state signatures associated with tissue-specific gene expression and enhancer activity in the embryonic limb
Cotney J, Leng J, Oh S, DeMare LE, Reilly SK, Gerstein MB, Noonan JP. Chromatin state signatures associated with tissue-specific gene expression and enhancer activity in the embryonic limb. Genome Research 2012, 22: 1069-1080. PMID: 22421546, PMCID: PMC3371702, DOI: 10.1101/gr.129817.111.Peer-Reviewed Original ResearchConceptsTissue-specific gene expressionChromatin state signatureActive developmental enhancersChromatin stateDevelopmental enhancersGene expressionEmbryonic tissuesHistone modification profilingOpen chromatin stateGenome-wide profilingEmbryonic cell typesMultiple embryonic tissuesGene expression differencesWhole transcriptome analysisH3K27me3 depletionEmbryonic forelimbChromatin profilingNucleosome displacementPutative enhancersEmbryonic limbMammalian embryosH3K27ac enrichmentRegulatory sequencesRegulatory elementsEnhancer discovery
2008
Human-Specific Gain of Function in a Developmental Enhancer
Prabhakar S, Visel A, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Morrison H, FitzPatrick DR, Afzal V, Pennacchio LA, Rubin EM, Noonan JP. Human-Specific Gain of Function in a Developmental Enhancer. Science 2008, 321: 1346-1350. PMID: 18772437, PMCID: PMC2658639, DOI: 10.1126/science.1159974.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBinding SitesBody PatterningConserved SequenceEmbryonic DevelopmentEnhancer Elements, GeneticEvolution, MolecularExtremitiesGene Expression ProfilingGene Expression Regulation, DevelopmentalHumansLimb BudsMacaca mulattaMiceMice, TransgenicMolecular Sequence DataMutationPan troglodytesPAX9 Transcription FactorSelection, GeneticTranscription FactorsConceptsExpression domainsHuman-specific substitutionsHuman-specific gainsGain of functionOrthologous elementsDevelopmental enhancersAncestral stateGene regulationNoncoding sequencesTerrestrial vertebratesHuman enhancersSynthetic enhancersEnhancer sequencesGene expressionRegulatory functionsDevelopmental stagesVivo analysisEnhancerVivo evidenceTransgenic miceSequenceVertebratesDomainRegulationSubstitution