2023
Transcription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape
Boddu P, Gupta A, Roy R, Herrero A, Verma A, Neugebauer K, Pillai M. Transcription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape. Blood 2023, 142: 709. DOI: 10.1182/blood-2023-188083.Peer-Reviewed Original ResearchChromatin organizationSuch epigenetic changesGenome editing approachesRNA splicing factorsChromatin landscapeSingle mutant alleleEpigenetic landscapeGenomic integrityTranscription defectTranscription kineticsSplicing factorsChIP-seqEpigenetic regulatorsEpigenetic changesEpigenetic therapyMutant allelesEditing approachesFactor mutationsK562 cell lineDownstream effectsCell linesMyeloid disordersClonal myeloid disordersHDAC pathwayMutations
2022
ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner
Xu X, Chan A, Li M, Liu Q, Mattson N, Pokharel S, Chang W, Yuan Y, Wang J, Moore R, Pirrotte P, Wu J, Su R, Müschen M, Rosen S, Chen J, Yang L, Chen C. ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner. Science Advances 2022, 8: eadc8911. PMID: 36563143, PMCID: PMC9788768, DOI: 10.1126/sciadv.adc8911.Peer-Reviewed Original ResearchCell cycle signalingCRISPR interference screenCell cycle machineryHallmark of tumorigenesisINO80 chromatinInterference screenEpigenetic regulatorsTumor progressionEpigenetic mechanismsCycle machineryEpigenetic dysregulationComplex membersTumor suppressorCell cycleCRISPR geneHCC tumor growthIes6CDKN2A expressionPharmacological inhibitionSignalingMultiple cancersHCC proliferationNovel opportunitiesTumor growthDynamic interplayHuman WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation
Cai WL, Chen JF, Chen H, Wingrove E, Kurley SJ, Chan LH, Zhang M, Arnal-Estape A, Zhao M, Balabaki A, Li W, Yu X, Krop ED, Dou Y, Liu Y, Jin J, Westbrook TF, Nguyen DX, Yan Q. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. ELife 2022, 11: e78163. PMID: 36043466, PMCID: PMC9584608, DOI: 10.7554/elife.78163.Peer-Reviewed Original ResearchConceptsBreast cancer cellsMetastatic breast cancerBreast cancerRibosomal gene expressionCancer cellsKnockdown of WDR5Vivo genetic screenReversible epigenetic mechanismsGenetic screenTranslation regulationTriple-negative breast cancerEpigenetic regulatorsEpigenetic mechanismsBreast cancer growthCancer-related deathTranslation efficiencyWDR5Novel therapeutic strategiesTranslation rateGene expressionCell growthAdvanced diseaseEffective therapyMetastatic capabilityPotent suppression193 Arachnoid Cysts as Genetically-encoded Harbingers of Neurodevelopmental Pathology
Kundishora A, Kiziltug E, Allington G, Allocco A, Smith H, Ocken J, Moreno-De-Luca A, DiLuna M, Jin S, Kahle K. 193 Arachnoid Cysts as Genetically-encoded Harbingers of Neurodevelopmental Pathology. Neurosurgery 2022, 68: 58-58. DOI: 10.1227/neu.0000000000001880_193.Peer-Reviewed Original ResearchGene expressionGene setsScRNAseq datasetsWhole-exome sequencingSingle-cell RNA sequencing dataExome-wide significanceCell type relationshipsMultiple epigenetic regulatorsRNA sequencing dataMulti-omics approachExome sequencingChromatin remodelingEpigenetic regulationMRNA processingPhenomic analysisEpigenetic regulatorsPhenomics techniquesIntegrative genomicsSequencing dataSignificant enrichmentGenesFirst insightPhenotypic clustersNovo variantsNovel associations
2021
PDE4D And HCN1 Ultrastructure In Rhesus Macaque Entorhinal Cortex: Relevance For Aging And Alzheimer's Disease
Datta D, Mentone S, Arnsten A. PDE4D And HCN1 Ultrastructure In Rhesus Macaque Entorhinal Cortex: Relevance For Aging And Alzheimer's Disease. Innovation In Aging 2021, 5: 638-639. PMCID: PMC8681434, DOI: 10.1093/geroni/igab046.2410.Peer-Reviewed Original ResearchDNA CpG methylationProtein mass spectrometrySomatic mutationsAge-related molecular changesSimilar genetic backgroundEpigenetic regulatorsCpG methylationEpigenetic alterationsWhole-exome sequencingMolecular damageGenetic backgroundDNAmeMolecular changesPostmortem brain samplesBrain samplesAbstract AgingSame brain samplesAlzheimer's diseaseCurrent understandingBiological agingBinding propertiesMutationsMass spectrometryMajor risk factorEpigeneticsSingle-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response
Johnson K, Anderson K, Courtois E, Gujar A, Barthel F, Varn F, Luo D, Seignon M, Yi E, Kim H, Estecio M, Zhao D, Tang M, Navin N, Maurya R, Ngan C, Verburg N, de Witt Hamer P, Bulsara K, Samuels M, Das S, Robson P, Verhaak R. Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response. Nature Genetics 2021, 53: 1456-1468. PMID: 34594038, PMCID: PMC8570135, DOI: 10.1038/s41588-021-00926-8.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCell PlasticityClonal EvolutionDNA Copy Number VariationsDNA MethylationEpigenesis, GeneticGene Expression Regulation, NeoplasticGenetic HeterogeneityGenome, HumanGliomaHumansMutationPhylogenyPromoter Regions, GeneticSingle-Cell AnalysisStress, PhysiologicalTumor MicroenvironmentConceptsDNA methylation disorderEnvironmental stress responsesMethylation disordersEnvironmental stress response pathwaysStress responseStress response processesStress response pathwaysSingle-cell transcriptomesDNA methylation changesDNA methylation differencesDNA methylation dataMulti-omics profilesDNA methylomeTranscriptional disruptionEpigenetic instabilityEpigenetic heterogeneityEpigenetic regulatorsResponse pathwaysCellular plasticityMethylation changesMethylation differencesCell statesMethylation dataIrradiation stressWild-type gliomasTargeting the Atf7ip–Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity
Hu H, Khodadadi-Jamayran A, Dolgalev I, Cho H, Badri S, Chiriboga LA, Zeck B, De Rodas Gregorio M, Dowling CM, Labbe K, Deng J, Chen T, Zhang H, Zappile P, Chen Z, Ueberheide B, Karatza A, Han H, Ranieri M, Tang S, Jour G, Osman I, Sucker A, Schadendorf D, Tsirigos A, Schalper KA, Velcheti V, Huang HY, Jin Y, Ji H, Poirier JT, Li F, Wong KK. Targeting the Atf7ip–Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity. Cancer Immunology Research 2021, 9: 1298-1315. PMID: 34462284, PMCID: PMC9414288, DOI: 10.1158/2326-6066.cir-21-0543.Peer-Reviewed Original ResearchConceptsHistone lysine methyltransferase 1Common adaptive mechanismSuppressor screenChromatin modifiersIntron retentionSET domainEpigenetic regulatorsEpigenetic modificationsEpigenetic modifiersType I interferon responseMethyltransferase 1I interferon responseHuman cancersTranscription factor 7Immune invasionInterferon responseAdaptive mechanismsFactor 7GenesCritical roleExpressionImmune evasionRejection of cellsAntigen processingAntigen expression
2020
Cancer Epigenetics, Tumor Immunity, and Immunotherapy
Cao J, Yan Q. Cancer Epigenetics, Tumor Immunity, and Immunotherapy. Trends In Cancer 2020, 6: 580-592. PMID: 32610068, PMCID: PMC7330177, DOI: 10.1016/j.trecan.2020.02.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune responseAntitumor immune responseCancer-immunity cycleAnticancer immune responseEpigenetic targeting agentsImpaired immunosurveillanceCurrent immunotherapiesTumor immunityImmunomodulatory drugsImmune cellsImmune restrictionTargeting agentEpigenetic mechanismsEpigenetic regulatorsImmunotherapyPharmaceutical modulationEpigenetic therapyTumorsImmunosurveillanceTherapyCurrent advancesDNA methylationImmunityResponse
2019
Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression
Tsankov AM, Wadsworth MH, Akopian V, Charlton J, Allon SJ, Arczewska A, Mead BE, Drake RS, Smith ZD, Mikkelsen TS, Shalek AK, Meissner A. Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression. Development 2019, 146: dev174722. PMID: 31515224, PMCID: PMC6803377, DOI: 10.1242/dev.174722.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell DifferentiationDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEnhancer Elements, GeneticEntropyGene Expression Regulation, DevelopmentalHuman Embryonic Stem CellsHumansMaleRepressor ProteinsRNA, MessengerTranscription, GeneticConceptsGlobal methylation levelsTranscriptional repressionSingle-cell RNA-sequencing dataMethylation levelsNew cell fatesMaintenance of pluripotencyHuman embryonic stem cellsMethylation of cytosineRNA-sequencing dataCell-cell variabilityStem cellsEmbryonic stem cellsHuman pluripotent stem cellsDNA methyltransferase activityMRNA expression dataPluripotent stem cellsTranscriptional variabilityMethyltransferases Dnmt3aCell fateEpigenetic regulatorsMethyltransferase DNMT3AExtrinsic signalsHigh-resolution viewMethyltransferase activityProper differentiationIntegrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma
Hlady RA, Sathyanarayan A, Thompson JJ, Zhou D, Wu Q, Pham K, Lee J, Liu C, Robertson KD. Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma. Hepatology 2019, 69: 639-652. PMID: 30136421, PMCID: PMC6351162, DOI: 10.1002/hep.30211.Peer-Reviewed Original ResearchConceptsHistone modification profilesPromoter/enhancer functionGenome-wide assessmentTranscription of genesEpigenetic marksHistone modificationsEpigenome deregulationEpigenetic regulatorsBioinformatics strategyEpigenetic mechanismsModification profilesEpigenetic underpinningsLiver epigenomeEpigenetic profilesEnhancer functionEpigenetic parametersEpigenomeDecrease cell viabilityDriver lociSignificant deregulationCancer initiationTranscriptionHuman cancersCancer cell linesCell lines
2018
Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer
Weng W, Liu N, Toiyama Y, Kusunoki M, Nagasaka T, Fujiwara T, Wei Q, Qin H, Lin H, Ma Y, Goel A. Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer. Molecular Cancer 2018, 17: 16. PMID: 29382334, PMCID: PMC5791351, DOI: 10.1186/s12943-018-0767-3.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overApoptosisBiomarkers, TumorCell DeathCell ProliferationColorectal NeoplasmsDisease ProgressionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingOncogenesPrognosisRNA InterferenceRNA, Small InterferingConceptsPIWI-interacting RNAsSmall RNA sequencingGene expression profiling resultsImportant epigenetic regulatorsDownstream target genesExpression profiling resultsCell survival pathwaysColorectal cancerPotential prognostic biomarkerTumor suppressor genePrognostic biomarkerEpigenetic regulatorsSequence complementarityNoncoding RNAsRNA sequencingTarget genesExpression profilingBiological functionsGene expressionSurvival pathwaysSuppressor geneClinical significanceDirect targetNovel oncogeneOncogenic mediators
2016
MicroRNAs in Control of Stem Cells in Normal and Malignant Hematopoiesis
Roden C, Lu J. MicroRNAs in Control of Stem Cells in Normal and Malignant Hematopoiesis. Current Stem Cell Reports 2016, 2: 183-196. PMID: 27547713, PMCID: PMC4988405, DOI: 10.1007/s40778-016-0057-1.Peer-Reviewed Original ResearchHematopoietic stem cellsStem cellsPost-transcriptional gene regulation mechanismSpecific gene expression programsPost-transcriptional gene expressionSmall non-coding RNAsGene expression programsLeukemia stem cellsGene regulation mechanismsFunction of miRNAsNon-coding RNAsStudy of miRNAsRole of miRNAsCell signaling pathwaysLSC biologyCancer stem cell conceptStem cell fieldEpigenetic machineryExpression programsHSC emergenceEpigenetic programsStem cell conceptEpigenetic regulatorsDifferentiated progenyHSC nicheRegulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family
Hysolli E, Tanaka Y, Su J, Kim KY, Zhong T, Janknecht R, Zhou XL, Geng L, Qiu C, Pan X, Jung YW, Cheng J, Lu J, Zhong M, Weissman SM, Park IH. Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family. Stem Cell Reports 2016, 7: 43-54. PMID: 27373925, PMCID: PMC4945581, DOI: 10.1016/j.stemcr.2016.05.014.Peer-Reviewed Original ResearchConceptsDNA methylation stateEmbryonic stem cellsInduced pluripotent stem cellsHuman somatic cell reprogrammingSomatic cell reprogrammingMethylation stateCell reprogrammingMiR-29 familyDNA methylation landscapeImportant epigenetic regulatorsStem cellsOverexpression of Oct4Global DNA methylationMiRNA-based approachesPluripotent stem cellsMethylation landscapeHistone modificationsDNA demethylationEpigenomic changesEarly reprogrammingEpigenetic regulatorsEpigenetic differencesDNA methylationHydroxymethylation analysisReprogramming
2015
Noncoding RNAs and neurobehavioral mechanisms in psychiatric disease
Kocerha J, Dwivedi Y, Brennand K. Noncoding RNAs and neurobehavioral mechanisms in psychiatric disease. Molecular Psychiatry 2015, 20: 677-684. PMID: 25824307, PMCID: PMC4440836, DOI: 10.1038/mp.2015.30.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPsychiatric diseasesPost-genome sequencing eraNew epigenetic targetsPotent epigenetic regulatorHuman Genome ProjectAttractive therapeutic potentialMicroRNA (miRNA) classNcRNA classesMajor neuronal pathwaysEpigenetic regulatorsSequencing eraEpigenetic targetsNoncoding RNAsGenome ProjectNeuronal pathwaysMultifactorial originPsychiatric disordersSingle proteinTherapeutic potentialReported rolesTherapeutic investigationsPleiotropic capacitySingle neuronsNeurobehavioral phenotypesDisease
2013
Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity
Liu R, Jin Y, Tang WH, Qin L, Zhang X, Tellides G, Hwa J, Yu J, Martin KA. Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity. Circulation 2013, 128: 2047-2057. PMID: 24077167, PMCID: PMC3899790, DOI: 10.1161/circulationaha.113.002887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCell DifferentiationCells, CulturedDioxygenasesDNA-Binding ProteinsEpigenesis, GeneticHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNuclear ProteinsPromoter Regions, GeneticProto-Oncogene ProteinsTrans-ActivatorsWound HealingConceptsTen-Eleven Translocation-2SMC differentiationTET2 knockdownSmooth muscle cellsGene expressionTranslocation 2Smooth Muscle Cell PlasticityMaster epigenetic regulatorSMC gene expressionContractile gene expressionMuscle cell plasticityDedifferentiated smooth muscle cellsTET2 overexpressionContractile smooth muscle cellsHuman smooth muscle cellsChromatin accessibilityEpigenetic landscapeSMC plasticityChromatin immunoprecipitationEpigenetic regulatorsEpigenetic mechanismsCell plasticityMaster regulatorSMC phenotypeTranscriptional upregulation
2012
Structural Insight into Coordinated Recognition of Trimethylated Histone H3 Lysine 9 (H3K9me3) by the Plant Homeodomain (PHD) and Tandem Tudor Domain (TTD) of UHRF1 (Ubiquitin-like, Containing PHD and RING Finger Domains, 1) Protein*
Cheng J, Yang Y, Fang J, Xiao J, Zhu T, Chen F, Wang P, Li Z, Yang H, Xu Y. Structural Insight into Coordinated Recognition of Trimethylated Histone H3 Lysine 9 (H3K9me3) by the Plant Homeodomain (PHD) and Tandem Tudor Domain (TTD) of UHRF1 (Ubiquitin-like, Containing PHD and RING Finger Domains, 1) Protein*. Journal Of Biological Chemistry 2012, 288: 1329-1339. PMID: 23161542, PMCID: PMC3543016, DOI: 10.1074/jbc.m112.415398.Peer-Reviewed Original ResearchConceptsTandem Tudor domainHistone H3 lysine 9Plant homeodomainH3 lysine 9Tudor domainHistone methylationLysine 9DNA methylationStructural insightsDNA replication forksCoordinated recognitionImportant epigenetic regulatorsUnmodified histone H3Unmodified H3UHRF1 proteinReplication forksHistone H3Epigenetic regulatorsLys-9Autoubiquitination activityLys-4H3K9me3UHRF1Linker regionBiochemical experiments
2008
A Mutation in the Mouse Chd2 Chromatin Remodeling Enzyme Results in a Complex Renal Phenotype
Marfella CG, Henninger N, LeBlanc SE, Krishnan N, Garlick DS, Holzman LB, Imbalzano AN. A Mutation in the Mouse Chd2 Chromatin Remodeling Enzyme Results in a Complex Renal Phenotype. Kidney & Blood Pressure Research 2008, 31: 421-432. PMID: 19142019, PMCID: PMC2818461, DOI: 10.1159/000190788.Peer-Reviewed Original ResearchConceptsChd2 proteinATP-dependent chromatin remodelingChromodomain helicase DNA-binding protein 2DNA-binding protein 2Family of enzymesChromatin remodelingChromatin structureEpigenetic regulatorsGlomerular diseaseGene expressionMolecular mechanismsKidney functionProtein 2Enzyme resultsDiverse groupProteinNew insightsMutationsRenal phenotypeKidney failureGlomerular functionHematocrit levelsNew moleculesSerum analysisMice
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