2024
Massively parallel disruption of enhancers active in human neural stem cells
Geller E, Noble M, Morales M, Gockley J, Emera D, Uebbing S, Cotney J, Noonan J. Massively parallel disruption of enhancers active in human neural stem cells. Cell Reports 2024, 43: 113693. PMID: 38271204, PMCID: PMC11078116, DOI: 10.1016/j.celrep.2024.113693.Peer-Reviewed Original ResearchHuman neural stem cellsNeural stem cellsStem cellsProliferation phenotypeAssociated with neurodevelopmental disordersNeurodevelopmental disordersEnhanced disruptionHuman Accelerated RegionsNeural progenitor proliferationEffects of genetic variationHuman cortical evolutionProgenitor proliferationSelf-renewalNeural progenitorsProgenitor populationsCerebral cortexChromatin interactionsHuman cerebral cortexNeural progenitor populationsGene regulationRegulatory elementsConserved regionGene disruptionGenetic variationRegulatory relationships
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 ResearchConceptsHuman-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
2015
The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment
Cotney J, Muhle RA, Sanders SJ, Liu L, Willsey AJ, Niu W, Liu W, Klei L, Lei J, Yin J, Reilly SK, Tebbenkamp AT, Bichsel C, Pletikos M, Sestan N, Roeder K, State MW, Devlin B, Noonan JP. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nature Communications 2015, 6: 6404. PMID: 25752243, PMCID: PMC4355952, DOI: 10.1038/ncomms7404.Peer-Reviewed Original ResearchConceptsASD risk genesRisk genesRegulatory networksAncient gene regulatory networksHuman neural stem cellsLoss of CHD8Specific regulatory networksGene regulatory networksCo-expression networkAutism risk genesEmbryonic mouse cortexChromatin modifiersIdentification of recurrentChromodomain-HelicaseChd8 knockdownNeural stem cellsMouse neurodevelopmentCHD8Human brain developmentFunction mutationsGenesStem cellsHuman neurodevelopmentNovo lossBrain development
2014
Evolution of Gene Regulation in Humans
Reilly S, Noonan J. Evolution of Gene Regulation in Humans. Annual Review Of Genomics And Human Genetics 2014, 17: 1-23. DOI: 10.1146/annurev-genom-090314-045935.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsRegulatory functionsGene regulationHuman-specific genetic changesGenetic changesNovel human phenotypeNew regulatory functionInduced pluripotent stem cellsPluripotent stem cellsUnique biological featuresSpecific regulatory changesHomologous humanGenome editingGene expressionHuman phenotypesFinal online publication datePrimate cellsHuman evolutionRegulatory activityStem cellsOnline publication dateExpression levelsNonhuman primate cellsBiological featuresRegulationRegulatory innovation
2013
The 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
2011
Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing
Ayoub AE, Oh S, Xie Y, Leng J, Cotney J, Dominguez MH, Noonan JP, Rakic P. Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 14950-14955. PMID: 21873192, PMCID: PMC3169109, DOI: 10.1073/pnas.1112213108.Peer-Reviewed Original ResearchConceptsTranscriptional programsHigh-resolution transcriptome mapDifferential transcriptome analysisStem cell maintenanceUnderlying transcriptional programsTransient embryonic zonesUncharacterized genesTranscriptome mapTranscriptome analysisEmbryonic mouse forebrainCell maintenanceGenetic programEmbryonic zonesMRNA sequencingCerebral cortexMolecular pathwaysStem cellsCell populationsMouse forebrainTranscriptsCortical plateSubventricular zoneGenesSequencingCortex