2012
Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis
Zhang P, Huang A, Morales-Ruiz M, Starcher BC, Huang Y, Sessa WC, Niklason LE, Giordano FJ. Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis. Human Gene Therapy 2012, 23: 1186-1199. PMID: 22891920, PMCID: PMC3498887, DOI: 10.1089/hum.2011.201.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAortic Stenosis, SupravalvularCell LineCell MovementCell ProliferationDosage Compensation, GeneticElastinGene ExpressionGene Expression RegulationHaploinsufficiencyHumansMutationNonsense Mediated mRNA DecayOrgan SpecificityProtein EngineeringTranscriptional ActivationWilliams SyndromeZinc FingersConceptsZinc finger protein transcription factorsTranscriptional activationWild-type alleleWilliams-Beuren syndromeMutant allelesEngineered Zinc Finger ProteinsElastin geneTargeted transcriptional activationCompensatory expressionSplice variantsZinc finger proteinProtein transcription factorsNonsense-mediated decayWild-type cellsMultiple splice variantsElastin expressionGene replacement strategyMutant proteinsHaploinsufficient genesTranscription factorsComplex genesNatural stoichiometryDistinct genetic syndromesGenesGenetic diseasesA Designed Zinc-finger Transcriptional Repressor of Phospholamban Improves Function of the Failing Heart
Zhang HS, Liu D, Huang Y, Schmidt S, Hickey R, Guschin D, Su H, Jovin IS, Kunis M, Hinkley S, Liang Y, Hinh L, Spratt SK, Case CC, Rebar EJ, Ehrlich BE, Ehrlich B, Gregory P, Giordano F. A Designed Zinc-finger Transcriptional Repressor of Phospholamban Improves Function of the Failing Heart. Molecular Therapy 2012, 20: 1508-1515. PMID: 22828502, PMCID: PMC3412484, DOI: 10.1038/mt.2012.80.Peer-Reviewed Original ResearchConceptsHeart failureZinc finger protein transcription factorsSingle gene regulationZinc finger transcriptional repressorDiverse DNA sequencesProtein transcription factorsDisease-related genesDisease-related proteinsGene repressionZFP TFsTranscriptional repressorTranscription factorsDNA sequencesPotent repressionPLN expressionHuman diseasesRepressorContractile functionDrug targetsFailing HeartTherapeutic inhibitionAnimal modelsReuptake kineticsRepressionTherapeutic interventionsmiR-1 mediated suppression of Sorcin regulates myocardial contractility through modulation of Ca2+ signaling
Ali R, Huang Y, Maher SE, Kim RW, Giordano FJ, Tellides G, Geirsson A. miR-1 mediated suppression of Sorcin regulates myocardial contractility through modulation of Ca2+ signaling. Journal Of Molecular And Cellular Cardiology 2012, 52: 1027-1037. PMID: 22326846, DOI: 10.1016/j.yjmcc.2012.01.020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCalcium SignalingCalcium-Binding ProteinsCardiac VolumeCardiomyopathiesCell LineDEAD-box RNA HelicasesHeartHumansMaleMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutMicroRNAsMyocardial ContractionMyocardiumRibonuclease IIIRNA InterferenceRNA, Small InterferingUp-RegulationConceptsCardiac functionMiR-1Normal cardiac contractile functionEnd-stage cardiomyopathyCardiac contractile functionWild-type miceCalcium signalingExcitation-contraction couplingModulation of Ca2Cultured mouse cardiomyocytesAcute cardiomyopathyMiR-1 targetsHeart failureMyocardial contractilityMiR-1 knockdownContractile functionAntagomir treatmentSorcin expressionCalcium homeostasisKnockdown miceSorcin levelsCardiac phenotypeMouse cardiomyocytesCritical mediatorPathological relevance
2007
The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity*
Luan Y, Yu XP, Xu K, Ding B, Yu J, Huang Y, Yang N, Lengyel P, Di Cesare PE, Liu CJ. The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity*. Journal Of Biological Chemistry 2007, 282: 16860-16870. PMID: 17439944, DOI: 10.1074/jbc.m610943200.Peer-Reviewed Original ResearchConceptsGene activationTranscription factorsRetinoblastoma proteinProtein-protein interactionsChromatin immunoprecipitation assaysMesenchymal cell lineSkeletal muscle myotubesP204 expressionP204 proteinCore-binding factor alpha1Numerous proteinsImmunoprecipitation assaysSuch mutantsOsteocalcin geneReporter geneGene expressionAntisense RNAMuscle myotubesOsteoblast differentiationCbfa1Factor alpha1ProteinEssential mediatorTernary complexCell lines