2024
Binding profiles for 961 Drosophila and C. elegans transcription factors reveal tissue-specific regulatory relationships.
Kudron M, Gevirtzman L, Victorsen A, Lear B, Gao J, Xu J, Samanta S, Frink E, Tran-Pearson A, Huynh C, Vafeados D, Hammonds A, Fisher W, Wall M, Wesseling G, Hernandez V, Lin Z, Kasparian M, White K, Allada R, Gerstein M, Hillier L, Celniker S, Reinke V, Waterston R. Binding profiles for 961 Drosophila and C. elegans transcription factors reveal tissue-specific regulatory relationships. Genome Research 2024, 34: 2319-2334. PMID: 39438113, PMCID: PMC11694743, DOI: 10.1101/gr.279037.124.Peer-Reviewed Original ResearchHigh-occupancy targetC. elegans transcription factorsSingle cell RNA-seq dataRegulatory relationshipsTranscription factor (TFChromatin immunoprecipitation sequencing dataTF-target relationshipsChIP-seq dataConsensus sequence motifRNA-seq dataDrosophila melanogaster</i>Promote target gene expressionTarget gene expressionChIP-seqSequence motifsSequence dataRegulatory networksEvents in vivoStock CenterModel organismsTranscription factorsTF functionGene expressionBinding sitesCell typesAntisense oligonucleotides and their applications in rare neurological diseases
McDowall S, Aung-Htut M, Wilton S, Li D. Antisense oligonucleotides and their applications in rare neurological diseases. Frontiers In Neuroscience 2024, 18: 1414658. PMID: 39376536, PMCID: PMC11456401, DOI: 10.3389/fnins.2024.1414658.Peer-Reviewed Original ResearchAntisense oligonucleotidesRare diseaseImpaired quality of lifeDuchenne muscular dystrophyRare neurological diseasesNeurological diseasesClinical trial designSpinal muscular atrophyRare conditionApplication of antisense oligonucleotidesHigh treatment costsTherapeutic antisense oligonucleotidesClinical trialsAnimal modelsMuscular dystrophyEffective treatmentQuality of lifeImpaired qualityMuscular atrophyAntisense oligomersTrial designTherapeutic validityTarget gene expressionDiseaseTreatment costsInhibition of GSK3α,β rescues cognitive phenotypes in a preclinical mouse model of CTNNB1 syndrome
Alexander J, Vazquez-Ramirez L, Lin C, Antonoudiou P, Maguire J, Wagner F, Jacob M. Inhibition of GSK3α,β rescues cognitive phenotypes in a preclinical mouse model of CTNNB1 syndrome. EMBO Molecular Medicine 2024, 16: 2109-2131. PMID: 39103699, PMCID: PMC11393422, DOI: 10.1038/s44321-024-00110-5.Peer-Reviewed Original ResearchHeterozygous loss-of-function variantsLoss-of-function variantsWnt signal transductionWnt target gene expressionSynaptic adhesion complexesTarget gene expressionB-cateninCognitive phenotypesHeterozygous mouse linePreclinical mouse modelsWild-type littermatesBrain functionAdhesion complexesSignal transductionEfficacious treatmentNeuronal functional propertiesRegulation of changesGene expressionMotor deficitsHeterozygous miceN-cadherinNa/K-ATPaseBrainMotor disabilityMouse model
2022
Histone H3 proline 16 hydroxylation regulates mammalian gene expression
Liu X, Wang J, Boyer J, Gong W, Zhao S, Xie L, Wu Q, Zhang C, Jain K, Guo Y, Rodriguez J, Li M, Uryu H, Liao C, Hu L, Zhou J, Shi X, Tsai Y, Yan Q, Luo W, Chen X, Strahl B, von Kriegsheim A, Zhang Q, Wang G, Baldwin A, Zhang Q. Histone H3 proline 16 hydroxylation regulates mammalian gene expression. Nature Genetics 2022, 54: 1721-1735. PMID: 36347944, PMCID: PMC9674084, DOI: 10.1038/s41588-022-01212-x.Peer-Reviewed Original ResearchConceptsPost-translational modificationsHistone post-translational modificationsMammalian gene expressionGene expressionHistone H3Mammalian cellsDNA-templated processesTranscriptome-wide analysisTarget gene expressionHydroxylation of prolineWnt/β-cateninChromatin recruitmentHistone codeTarget genesRegulatory marksLysine residuesDirect bindingTriple-negative breast cancerΒ-cateninResidues 16H3ExpressionH3K4me3TrimethylationGenomeHigh Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells
Deng H, Schwartz MA. High Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells. Journal Of The American Heart Association 2022, 11: e025337. PMID: 35861829, PMCID: PMC9707828, DOI: 10.1161/jaha.121.025337.Peer-Reviewed Original ResearchConceptsInflammatory cytokinesSmad2/3 activationEndothelial cellsNuclear translocationInflammatory cytokine treatmentGrowth factor betaVascular endothelial cellsQuantitative polymerase chain reactionSmad2/3 nuclear translocationTarget gene expressionBackground AtherosclerosisInflammatory mediatorsInflammatory pathwaysPolymerase chain reactionResult of inhibitionCytokine treatmentInhibits CytokineFactor betaMesenchymal transitionHigh fluid shear stressCytokinesEndMTGene expressionLaminar fluid shear stressFluid shear stressPPARγ phase separates with RXRα at PPREs to regulate target gene expression
Li Z, Luo L, Yu W, Li P, Ou D, Liu J, Ma H, Sun Q, Liang A, Huang C, Chi T, Huang X, Zhang Y. PPARγ phase separates with RXRα at PPREs to regulate target gene expression. Cell Discovery 2022, 8: 37. PMID: 35473936, PMCID: PMC9043196, DOI: 10.1038/s41421-022-00388-0.Peer-Reviewed Original ResearchPPAR response elementNuclear condensatesTranscriptional activationPPRE siteZinc finger motifsDNA binding domainsKey transcription activatorSpecific transcriptional activationTarget gene expressionPPARγ/RXRαRetinoid X receptor αPPARγ target genesFinger motifPhase-separated dropletsTranscription activatorTranscriptional responseObligate heterodimersTarget genesX receptor αBinding domainsGene expressionResponse elementPeroxisome proliferator-activated receptorNovel mechanismProliferator-activated receptor
2021
DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis
Laut C, Leasure C, Pi H, Carlin S, Chu M, Hillebrand G, Lin H, Yi X, Stauff D, Skaar E. DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis. Infection And Immunity 2021, 90: e00560-21. PMID: 34748369, PMCID: PMC8788696, DOI: 10.1128/iai.00560-21.Peer-Reviewed Original ResearchConceptsTwo-component systemGene expressionSubstrate-binding subunitSignal transduction activityTarget gene expressionB. anthracisBacillus anthracisGram-positive bacteriumHost-induced stressesClpXP proteaseProtein chaperonesSignal transductionClpXGene productsTransduction activityDnaJVertebrate hostsHeme levelsHomeostasis regulatorGenetic selectionHigh heme levelsCell envelope disruptionBioterror weaponHssRSAnthracisActivation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling
Deng H, Min E, Baeyens N, Coon BG, Hu R, Zhuang ZW, Chen M, Huang B, Afolabi T, Zarkada G, Acheampong A, McEntee K, Eichmann A, Liu F, Su B, Simons M, Schwartz MA. Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2105339118. PMID: 34504019, PMCID: PMC8449390, DOI: 10.1073/pnas.2105339118.Peer-Reviewed Original ResearchConceptsLow fluid shear stressFluid shear stressNuclear translocationSmad linker regionTransmembrane protein Neuropilin-1Target gene expressionCyclin-dependent kinasesBone morphogenetic proteinEC-specific deletionSmad2/3 nuclear translocationNuclear localizationHigh fluid shear stressLinker regionMorphogenetic proteinsGene expressionRegulatory mechanismsActivation of Smad2/3Receptor ALK5Smad2/3 phosphorylationTranslocationCell sensingEndothelial cell (EC) sensingPhosphorylationALK5Smad2/3
2016
Large-scale mapping of gene regulatory logic reveals context-dependent repression by transcriptional activators
van Dijk D, Sharon E, Lotan-Pompan M, Weinberger A, Segal E, Carey LB. Large-scale mapping of gene regulatory logic reveals context-dependent repression by transcriptional activators. Genome Research 2016, 27: 87-94. PMID: 27965290, PMCID: PMC5204347, DOI: 10.1101/gr.212316.116.Peer-Reviewed Original ResearchConceptsTranscription factorsGene regulatory logicPromoter DNA sequencesGene expression outputActive transcription factorTarget gene expressionGene expression profilesMaximum promoter activityTranscriptional activatorExpression outputRegulatory logicDNA sequencesGene expressionPromoter activityIntracellular signalsExpression profilesTF moleculesActivity of thousandsActivator siteLocal poolAbsolute expressionTF concentrationPromoterKey mediatorExpressionNovel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells
Sun B, Fiskus W, Zhang L, Raina K, Coleman K, Winkler J, Qian Y, Crew A, Shen A, Saenz D, Mill C, Wang M, Crews C, Bhalla K. Novel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells. Blood 2016, 128: 1058. DOI: 10.1182/blood.v128.22.1058.1058.Peer-Reviewed Original ResearchTarget gene expressionBruton's tyrosine kinaseC-MycARV-825Transcription factorsPrimary MCL cellsTranscriptional activityGene expressionTyrosine kinaseBcl-xLE3 ubiquitin ligase activityMCL cellsUbiquitin ligase activityHuman mantle cell lymphoma cellsB-cell receptor signalingCell receptor signalingBinding of BRD4Regulation of mRNAInk4a/ArfAcetylated chromatinCopy number gainsLigase activityHematopoietic progenitor cellsBET proteinsBETi treatmentNotch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6
Mouillesseaux KP, Wiley DS, Saunders LM, Wylie LA, Kushner EJ, Chong DC, Citrin KM, Barber AT, Park Y, Kim JD, Samsa LA, Kim J, Liu J, Jin SW, Bautch VL. Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6. Nature Communications 2016, 7: 13247. PMID: 27834400, PMCID: PMC5114582, DOI: 10.1038/ncomms13247.Peer-Reviewed Original ResearchConceptsBone morphogenetic proteinBMP responsivenessComplexities of BMPR-Smad phosphorylationSmad transcription factorsTarget gene expressionNotch-dependent regulationVessel growthBMP ligandsBMP inhibitorsTranscription factorsBMP2 ligandsMorphogenetic proteinsEndothelial cellsGene expressionSmad6 expressionLateral branchingNotch statusBlood vessel growthNuclear translocationBranch formationBind receptorsSmad6Vessel branchingCoordinated response
2015
Oxidative stress-responsive transcription factor NRF2 is not indispensable for the human hepatic Flavin-containing monooxygenase-3 (FMO3) gene expression in HepG2 cells
Rudraiah S, Gu X, Hines R, Manautou J. Oxidative stress-responsive transcription factor NRF2 is not indispensable for the human hepatic Flavin-containing monooxygenase-3 (FMO3) gene expression in HepG2 cells. Toxicology In Vitro 2015, 31: 54-59. PMID: 26616280, PMCID: PMC4695222, DOI: 10.1016/j.tiv.2015.11.016.Peer-Reviewed Original ResearchConceptsGene expressionFlavin-containing monooxygenasesStress-responsive transcription factor Nrf2Stress transcription factorsCytosolic regulatory proteinsHepG2 cellsPromoter-luciferase reporter constructsNrf2 target gene expressionGene regulation studiesCo-transfection studiesTarget gene expressionReporter gene activityHeme oxygenase-1Transcription factor Nrf2Luciferase reporter constructsTranscriptional regulationGene regulationKelch-like ECHGene activityTranscription factorsRegulatory proteinsRegulatory pathwaysReporter constructsExpression vectorRegulation studiesThe miR-199–dynamin regulatory axis controls receptor-mediated endocytosis
Aranda JF, Canfrán-Duque A, Goedeke L, Suárez Y, Fernández-Hernando C. The miR-199–dynamin regulatory axis controls receptor-mediated endocytosis. Journal Of Cell Science 2015, 128: 3197-3209. PMID: 26163491, PMCID: PMC4582188, DOI: 10.1242/jcs.165233.Peer-Reviewed Original ResearchConceptsClathrin heavy chainReceptor-mediated endocytosisIntracellular traffickingLow-density lipoprotein receptorGene expressionMiR-199aSmall non-coding RNAsNon-coding RNAsTarget gene expressionDynamin genesEukaryotic cellsHuman cell linesEndocytic transportGTPase familyCav-1 expressionUnexpected layerCaveolin-1Intronic sequencesIntracellular transportPhysiological processesEndocytosisImportant regulatorMiR-199bCell linesGenes
2014
DNA Demethylation By Activation-Induced Cytidine Deaminase in B Cell Lymphoma
Xi Y, Shivarov V, Yaari G, Kleinstein S, Strout M. DNA Demethylation By Activation-Induced Cytidine Deaminase in B Cell Lymphoma. Blood 2014, 124: 3549. DOI: 10.1182/blood.v124.21.3549.3549.Peer-Reviewed Original ResearchActivation-induced cytidine deaminaseDNA demethylationGene expressionDNA methylationMethylation sitesBisulfite sequencingBL2 cellsHumanHT-12 v4 Expression BeadChipPrimary transcriptional start sitesC-terminal deletion mutantsCpG sitesGenome-wide methylation profilingActive DNA demethylationMethylation statusRNA polymerase IISomatic cell differentiationCytidine deaminaseSingle-nucleotide resolutionTranscriptional start siteSubset of genesDNA repair pathwaysList of genesTarget gene expressionEarly cell developmentV4 Expression BeadChipLincRNA-p21 Activates p21 In cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpoint
Dimitrova N, Zamudio JR, Jong RM, Soukup D, Resnick R, Sarma K, Ward AJ, Raj A, Lee JT, Sharp PA, Jacks T. LincRNA-p21 Activates p21 In cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpoint. Molecular Cell 2014, 54: 777-790. PMID: 24857549, PMCID: PMC4103188, DOI: 10.1016/j.molcel.2014.04.025.Peer-Reviewed Original ResearchConceptsG1/S checkpointGene expressionS checkpointPolycomb target genesGlobal gene expressionP53 transcriptional networkTarget gene expressionTumor suppressor pathwayConditional knockout mouse modelP53 tumor suppressor pathwayChromatin stateTranscriptional networksKnockout mouse modelNeighboring genesMRNA translationProtein stabilityTarget genesP21 transcriptionSuppressor pathwayAdditional phenotypesGenesP21 levelsLincRNA-p21P21 expressionCoactivator
2013
A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression
Goedeke L, Vales-Lara FM, Fenstermaker M, Cirera-Salinas D, Chamorro-Jorganes A, Ramírez CM, Mattison JA, de Cabo R, Suárez Y, Fernández-Hernando C. A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression. Molecular And Cellular Biology 2013, 33: 2339-2352. PMID: 23547260, PMCID: PMC3648071, DOI: 10.1128/mcb.01714-12.Peer-Reviewed Original ResearchConceptsMiR-33Gene expressionRegulatory roleTarget gene networkKey transcriptional regulatorTarget gene expressionMetabolism gene expressionIntronic microRNAsHuman hepatic cellsLipid metabolismSterol regulatory element-binding protein 2Transcriptional regulatorsSister strandsGene networksLipid metabolism gene expressionSteady-state levelsHost genesFatty acid metabolismFatty acid oxidationKey enzymeLipid homeostasisPassenger strandMicroRNA-33Functional roleProtein 2
2012
First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy
Sen M, Thomas SM, Kim S, Yeh JI, Ferris RL, Johnson JT, Duvvuri U, Lee J, Sahu N, Joyce S, Freilino ML, Shi H, Li C, Ly D, Rapireddy S, Etter JP, Li PK, Wang L, Chiosea S, Seethala RR, Gooding WE, Chen X, Kaminski N, Pandit K, Johnson DE, Grandis JR. First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy. Cancer Discovery 2012, 2: 694-705. PMID: 22719020, PMCID: PMC3668699, DOI: 10.1158/2159-8290.cd-12-0191.Peer-Reviewed Original ResearchConceptsSTAT3 target genesTarget genesSTAT3 target gene expressionSTAT3-selective inhibitorsTarget gene expressionInhibited xenograft growthSelective STAT3 inhibitorSystemic administrationTranscription factor decoyTranscription factorsSTAT3 proteinBroader clinical developmentGene expressionPhase 0 trialsSTAT3 inhibitorHuman cancersSTAT3Expression levelsSTAT3 decoyCancer cellsCellular viabilityNeck cancerSaline controlsNeck tumorsHuman trialsInhibition of CD44 Gene Expression in Human Skin Models, Using Self-Delivery Short Interfering RNA Administered by Dissolvable Microneedle Arrays
Lara MF, González-González E, Speaker TJ, Hickerson RP, Leake D, Milstone LM, Contag CH, Kaspar RL. Inhibition of CD44 Gene Expression in Human Skin Models, Using Self-Delivery Short Interfering RNA Administered by Dissolvable Microneedle Arrays. Human Gene Therapy 2012, 23: 816-823. PMID: 22480249, PMCID: PMC3413896, DOI: 10.1089/hum.2011.211.Peer-Reviewed Original ResearchConceptsTransgenic mouse modelInhibition of CD44CD44-specific antibodiesCD44 mRNA levelsDissolvable microneedle arraysGene expressionMouse modelXenograft modelSkin disordersCD44 gene expressionHuman skin modelTarget cellsMRNA levelsHuman skin equivalentsKeratinocyte membraneTreatmentInhibitionStratum corneumTarget gene expressionSiRNASkin equivalentsEpidermal equivalentsMicroneedle arraysSkin modelExpression
2011
High Throughput Determination of TGFβ1/SMAD3 Targets in A549 Lung Epithelial Cells
Zhang Y, Handley D, Kaplan T, Yu H, Bais AS, Richards T, Pandit KV, Zeng Q, Benos PV, Friedman N, Eickelberg O, Kaminski N. High Throughput Determination of TGFβ1/SMAD3 Targets in A549 Lung Epithelial Cells. PLOS ONE 2011, 6: e20319. PMID: 21625455, PMCID: PMC3098871, DOI: 10.1371/journal.pone.0020319.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceCell LineChromatin ImmunoprecipitationDNA PrimersElectrophoretic Mobility Shift AssayEpithelial CellsHumansLungOligonucleotide Array Sequence AnalysisPromoter Regions, GeneticProtein BindingReverse Transcriptase Polymerase Chain ReactionSmad3 ProteinTransforming Growth Factor beta1ConceptsGene expression microarraysLung epithelial cellsMolecular pathwaysTranscriptional regulationExpression microarraysGlobal transcriptional regulationTGFβ1/Smad3Epithelial cellsHuman promoter regionsSignal transduction cascadeTarget gene expressionEpithelial cell phenotypeGene expression analysisTranscription factor Smad3Primary lung epithelial cellsSmad3 targetsQuantitative real-time RT-PCRFOXA2 promoterHuman A549 alveolar epithelial cellsChromatin immunoprecipitationTransduction cascadeTarget genesA549 lung epithelial cellsExpression analysisGene expression
2008
Going Nuclear Is Again a Winning (Wnt) Strategy
Zhong W. Going Nuclear Is Again a Winning (Wnt) Strategy. Developmental Cell 2008, 15: 635-636. PMID: 19000826, DOI: 10.1016/j.devcel.2008.10.012.Peer-Reviewed Original Research
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