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 ResearchConceptsHuman-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
2023
A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension
Gunawardhana K, Hong L, Rugira T, Uebbing S, Kucharczak J, Mehta S, Karunamuni D, Cabera-Mendoza B, Gandotra N, Scharfe C, Polimanti R, Noonan J, Mani A. A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension. Journal Of Clinical Investigation 2023, 133: e160036. PMID: 36602864, PMCID: PMC9927944, DOI: 10.1172/jci160036.Peer-Reviewed Original ResearchConceptsDevelopment of hypertensionParallel reporter assaysRenin inhibitor aliskirenNeural crest-derived cellsRenin-producing cellsSystems biology approachRNA-seq analysisCell-specific disruptionCrest-derived cellsSmooth muscle cellsMuscle cell proteinsSystemic hypertensionBlood pressureWT miceAntihypertensive drugsBiology approachSuper enhancersFine mappingWT littermatesThird intronMultiple GWASCollagen depositionMouse aortaReporter assaysFate mapping
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
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 developmentEvolutionary 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
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
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
2006
Accelerated Evolution of Conserved Noncoding Sequences in Humans
Prabhakar S, Noonan JP, Pääbo S, Rubin EM. Accelerated Evolution of Conserved Noncoding Sequences in Humans. Science 2006, 314: 786-786. PMID: 17082449, DOI: 10.1126/science.1130738.Peer-Reviewed Original ResearchConceptsNoncoding sequencesNeuronal cell adhesionConserved Noncoding SequencesCis-regulatory changesHuman-specific substitutionsCell adhesionHuman regulatory sequencesPhenotypic divergenceAdaptive substitutionsGene regulationAccelerated evolutionIndependent evolutionRegulatory sequencesAdhesion genesHuman evolutionNeuronal phenotypeDifferent neuronal phenotypesGenesSequenceSimilar enrichmentBrain developmentChimpanzeesEvolutionMammalsAdhesion