2024
HBI: a hierarchical Bayesian interaction model to estimate cell-type-specific methylation quantitative trait loci incorporating priors from cell-sorted bisulfite sequencing data
Cheng Y, Cai B, Li H, Zhang X, D’Souza G, Shrestha S, Edmonds A, Meyers J, Fischl M, Kassaye S, Anastos K, Cohen M, Aouizerat B, Xu K, Zhao H. HBI: a hierarchical Bayesian interaction model to estimate cell-type-specific methylation quantitative trait loci incorporating priors from cell-sorted bisulfite sequencing data. Genome Biology 2024, 25: 273. PMID: 39407252, PMCID: PMC11476968, DOI: 10.1186/s13059-024-03411-7.Peer-Reviewed Original ResearchConceptsMethylation quantitative trait lociQuantitative trait lociTrait lociMethylation dataFunctional annotation of genetic variantsAnnotation of genetic variantsGenetic variantsBisulfite sequencing dataEffects of genetic variantsBiologically relevant cell typesDNA methylation levelsCell typesFunctional annotationSequence dataComplex traitsMethylation datasetsRelevant cell typesMeQTLsMethylation levelsMethylation regulatorsReal data analysesLociVariantsMethylationDNAImproved methods for genetic manipulation of the alkaliphile Halalkalibacterium halodurans
Wencker F, Lyon S, Breaker R. Improved methods for genetic manipulation of the alkaliphile Halalkalibacterium halodurans. Frontiers In Microbiology 2024, 15: 1465811. PMID: 39360312, PMCID: PMC11445130, DOI: 10.3389/fmicb.2024.1465811.Peer-Reviewed Original ResearchDNA methylation profiles of cancer-related fatigue associated with markers of inflammation and immunometabolism
Xiao C, Peng G, Conneely K, Zhao H, Felger J, Wommack E, Higgins K, Shin D, Saba N, Bruner D, Miller A. DNA methylation profiles of cancer-related fatigue associated with markers of inflammation and immunometabolism. Molecular Psychiatry 2024, 30: 76-83. PMID: 38977918, DOI: 10.1038/s41380-024-02652-z.Peer-Reviewed Original ResearchGene expressionMethylation lociAssociated with gene expressionHead and neck cancerDNA methylation profilesProtein markersLipid metabolismInvolvement of genesIllumina MethylationEPICDNA methylationRelevant gene expressionEpigenetic modificationsExpression pairsInflammatory markersInflammatory responseLociHead and neck cancer patientsAssociated with inflammatory markersGenesDNAMarkers of inflammationAssociated with fatigueExpressionMethylationPost-radiotherapySingle-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA
Cheng J, Swarup N, Morselli M, Huang W, Aziz M, Caggiano C, Kordi M, Patel A, Chia D, Kim Y, Li F, Wei F, Zaitlen N, Krysan K, Dubinett S, Pellegrini M, Wong D. Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA. Nucleic Acids Research 2024, 52: e50-e50. PMID: 38797520, PMCID: PMC11194076, DOI: 10.1093/nar/gkae276.Peer-Reviewed Original ResearchTranscription start siteMethylation profilesCell-free DNAWhole-genome bisulfite sequencingCytosine methylation changesLevels of DNA methylationSingle-base resolutionUpstream transcription start siteBS-seqStart siteBisulfite sequencingCpG islandsDNA fragmentationBisulfite conversionMethylation changesDNA methylationBisulfite treatmentLarge DNAsMethylation analysisDNANon-cancer samplesBisulfiteFragmentsHemopoietic cellsMethylation
2023
Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use
Fang F, Quach B, Lawrence K, van Dongen J, Marks J, Lundgren S, Lin M, Odintsova V, Costeira R, Xu Z, Zhou L, Mandal M, Xia Y, Vink J, Bierut L, Ollikainen M, Taylor J, Bell J, Kaprio J, Boomsma D, Xu K, Sandler D, Hancock D, Johnson E. Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use. Molecular Psychiatry 2023, 29: 124-133. PMID: 37935791, PMCID: PMC11078760, DOI: 10.1038/s41380-023-02310-w.Peer-Reviewed Original ResearchEpigenome-wide association studiesDNA methylationCpG sitesDNA methylation changesEpigenome-wide associationSignificant CpG sitesMethylation changesBlood-based DNA methylationAssociation studiesSignificant CpGsEWAS analysisFalse discovery rateMethylationHealth outcomesLifetime cannabisCigarette smokingDiscovery rateMethylation scoreADGRF1APOBRACTN1SitesADAM12CpGEnvironmental exposuresLysine Demethylation in Pathogenesis
Cao J, Yan Q. Lysine Demethylation in Pathogenesis. Advances In Experimental Medicine And Biology 2023, 1433: 1-14. PMID: 37751133, DOI: 10.1007/978-3-031-38176-8_1.ChaptersConceptsLysine demethylasesLSD1/KDM1AHistone lysine methylationHistone lysine methyltransferasesMajor epigenetic mechanismsNormal developmentNon-histone substratesSpecific small molecule inhibitorsSmall molecule inhibitorsLysine methylationLysine methyltransferasesHistone methylationHistone lysineLysine demethylationEpigenetic mechanismsDNA repairArginine residuesHuman diseasesMore subfamiliesMolecule inhibitorsLysine modificationDemethylasesMethylationTreatment of cancerEnzymeAcetyl-methyllysine marks chromatin at active transcription start sites
Lu-Culligan W, Connor L, Xie Y, Ekundayo B, Rose B, Machyna M, Pintado-Urbanc A, Zimmer J, Vock I, Bhanu N, King M, Garcia B, Bleichert F, Simon M. Acetyl-methyllysine marks chromatin at active transcription start sites. Nature 2023, 622: 173-179. PMID: 37731000, PMCID: PMC10845139, DOI: 10.1038/s41586-023-06565-9.Peer-Reviewed Original ResearchConceptsPost-translational modificationsLysine residuesActive transcription start sitesTranscription start siteRange of speciesChromatin biologyChromatin proteinsLysine methylationActive chromatinProteins BRD2Transcriptional initiationLysine acetylationHistone H4Start siteMammalian tissuesHuman diseasesSame residuesMethylationAcetylationChromatinResiduesProteinBiological signalsHistonesBRD2Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits
Cheng Y, Justice A, Wang Z, Li B, Hancock D, Johnson E, Xu K. Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits. BMC Genomics 2023, 24: 556. PMID: 37730558, PMCID: PMC10510240, DOI: 10.1186/s12864-023-09661-2.Peer-Reviewed Original ResearchConceptsDNA methylationMultiple traitsPleiotropic effectsGenetic variantsAberrant DNA methylationPhenome-wide association studyCis-meQTLsComplex traitsRelevant traitsDNAm sitesEnrichment analysisMeQTLsAssociation studiesSignificant traitsTraitsImmune pathwaysMethylationNew insightsMendelian randomizationImmunological functionsGenesVariantsCausal rolePathwayCpGMolecular Techniques and Gene Mutations in Myelodysplastic Syndromes
Mendoza H, Siddon A. Molecular Techniques and Gene Mutations in Myelodysplastic Syndromes. Clinics In Laboratory Medicine 2023, 43: 549-563. PMID: 37865502, DOI: 10.1016/j.cll.2023.06.002.Peer-Reviewed Original ResearchMore than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome
Minteer C, Thrush K, Gonzalez J, Niimi P, Rozenblit M, Rozowsky J, Liu J, Frank M, McCabe T, Sehgal R, Higgins-Chen A, Hofstatter E, Pusztai L, Beckman K, Gerstein M, Levine M. More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome. Science Advances 2023, 9: eadf4163. PMID: 37467337, PMCID: PMC10355820, DOI: 10.1126/sciadv.adf4163.Peer-Reviewed Original ResearchConceptsStem cell divisionImmortalized human cellsTissue-specific cancer riskTumorigenic stateCell divisionDNA methylationEpigenetic changesAge-related accumulationHuman cellsMultiple tissuesSomatic mutationsClinical tissuesTissue differencesEpigenomeCellsTissueNormal tissuesMethylationMutationsReplicationNormal breast tissueSignaturesVitroAccumulationDivisionMETTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells
Xiao Z, Wang S, Tian Y, Lv W, Sheng H, Zhan M, Huang Q, Zhang Z, Zhu L, Zhu C, Zhong H, Wen Q, Liu Z, Tan J, Xu Y, Yang M, Liu Y, Flavell R, Yang Q, Cao G, Yin Z. METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells. Cell Reports 2023, 42: 112684. PMID: 37355989, DOI: 10.1016/j.celrep.2023.112684.Peer-Reviewed Original ResearchConceptsM6A methylationMRNA stabilityΓδ T17 cellsEndogenous double-stranded RNADouble-stranded RNAActivation of STAT1MRNA metabolismMRNA turnoverGene expressionKey enzymeDsRNA contentT17 cellsMethylationFunctional specializationRNA contentΓδ TCritical roleMETTL3Numerous aspectsCellsT17Distinct subsetsM6ATranscriptsRNA7SK methylation by METTL3 promotes transcriptional activity
Perez-Pepe M, Desotell A, Li H, Li W, Han B, Lin Q, Klein D, Liu Y, Goodarzi H, Alarcón C. 7SK methylation by METTL3 promotes transcriptional activity. Science Advances 2023, 9: eade7500. PMID: 37163588, PMCID: PMC10171809, DOI: 10.1126/sciadv.ade7500.Peer-Reviewed Original ResearchConceptsTranscriptional elongationTranscriptional responseAdaptive transcriptional responseHeterogeneous nuclear ribonucleoproteinsElongation factor complexPositive transcription elongation factor complexGrowth factorExtracellular signalsRNA modificationsRNA 7SKEpidermal growth factorCell signalingInduces phosphorylationMethyltransferase 3Nuclear ribonucleoproteinFactor complexTranscriptional activityUnknown functionMethylationMETTL3RibonucleoproteinPhosphorylationTEFbElongationSignalingEpigenome-Wide Meta-Analysis Reveals Differential DNA Methylation Associated With Estimated Glomerular Filtration Rate Among African American Men With HIV
Chen J, Hui Q, Wang Z, Wilson F, So-Armah K, Freiberg M, Justice A, Xu K, Zhao W, Ammous F, Smith J, Kardia S, Gwinn M, Marconi V, Sun Y. Epigenome-Wide Meta-Analysis Reveals Differential DNA Methylation Associated With Estimated Glomerular Filtration Rate Among African American Men With HIV. Kidney International Reports 2023, 8: 1076-1086. PMID: 37180517, PMCID: PMC10166785, DOI: 10.1016/j.ekir.2023.02.1085.Peer-Reviewed Original ResearchEpigenome-wide association studiesDNA methylationGlomerular filtration rateRenal diseaseFinger protein 20Differential DNA methylationKidney functionFiltration rateAfrican ancestryEnd-stage renal diseaseDifferent populationsProtein 20Ancestral groupsRenal disease progressionAssociation studiesDifferent ancestral groupsMethylationAfrican American menAncestryEuropean ancestryStudy cohortIndependent African American samplesDisease progressionFaster progressionGeneral populationThe Cutting Edge of Epigenetic Clocks: In Search of Mechanisms Linking Aging and Mental Health
Harvanek Z, Boks M, Vinkers C, Higgins-Chen A. The Cutting Edge of Epigenetic Clocks: In Search of Mechanisms Linking Aging and Mental Health. Biological Psychiatry 2023, 94: 694-705. PMID: 36764569, PMCID: PMC10409884, DOI: 10.1016/j.biopsych.2023.02.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis
Okuda K, Nakahara K, Ito A, Iijima Y, Nomura R, Kumar A, Fujikawa K, Adachi K, Shimada Y, Fujio S, Yamamoto R, Takasugi N, Onuma K, Osaki M, Okada F, Ukegawa T, Takeuchi Y, Yasui N, Yamashita A, Marusawa H, Matsushita Y, Katagiri T, Shibata T, Uchida K, Niu S, Lang N, Nakamura T, Zhang K, Lipton S, Uehara T. Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis. Nature Communications 2023, 14: 621. PMID: 36739439, PMCID: PMC9899281, DOI: 10.1038/s41467-023-36232-6.Peer-Reviewed Original ResearchConceptsS-nitrosylationDNA methyltransferasesEnzymatic activityGene expressionDe novo DNA methylationNovo DNA methylationAberrant S-nitrosylationProtein S-nitrosylationDNA methyltransferase 3BDNMT enzymatic activityStructure-based virtual screeningEpigenetic regulationDNA methylationCysteine residuesMethyltransferase 3BVivo cancer modelsS-adenosylAberrant upregulationNeoplastic cell proliferationHuman colonic adenomasMethylationCyclin D2Cell proliferationTumor formationDNMT3B
2022
PRMT4-mediated arginine methylation promotes tyrosine phosphorylation of VEGFR-2 and regulates filopodia protrusions
Hartsough E, Shelke R, Amraei R, Aryan Z, Lotfollahzadeh S, Rahimi N. PRMT4-mediated arginine methylation promotes tyrosine phosphorylation of VEGFR-2 and regulates filopodia protrusions. IScience 2022, 25: 104736. PMID: 35942094, PMCID: PMC9356023, DOI: 10.1016/j.isci.2022.104736.Peer-Reviewed Original ResearchSrc homology domain 2Protein arginine methyltransferase 4N-terminal domain bindsFilopodia protrusionsVEGFR-2Arginine methylationDomain bindsVascular endothelial growth factor receptor 2 activationSignal transductionTyrosine phosphorylationC-SrcMolecular mechanismsDomain 2MethylationPhosphorylationAngiogenic signalingPathological angiogenesisReceptor 2 activationAngiogenic responseTumor angiogenesisVEGFR-2 inhibitorsEVH1AngiogenesisTransductionSignalingInvestigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia
Xu K, Li S, Pandey P, Kang AY, Morimoto LM, Mancuso N, Ma X, Metayer C, Wiemels JL, de Smith AJ. Investigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia. Human Molecular Genetics 2022, 31: 3741-3756. PMID: 35717575, PMCID: PMC9616572, DOI: 10.1093/hmg/ddac137.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesSingle nucleotide polymorphismsGenetic risk lociDNA methylationRisk single nucleotide polymorphismsRisk lociAssociation studiesHeritable genetic variationGenome-wide association studiesMost single nucleotide polymorphismsDNA methylation differencesNon-European populationsEpigenetic mechanismsGenetic variationMethylation differencesSignificant DMPsPromoter regionFunctional pathwaysCpG positionsAssociation analysisFunctional roleMethylationNucleotide polymorphismsLociBlood DNAEpigenetic Epidemiology of Autism and Other Neurodevelopmental Disorders
Wang S, Jiang Y. Epigenetic Epidemiology of Autism and Other Neurodevelopmental Disorders. 2022, 405-426. DOI: 10.1007/978-3-030-94475-9_17.ChaptersEpigenome-wide association studiesAbnormal DNA methylationDNA methylationHistone modificationsTissue-specific patternsNeurodevelopmental disordersEpigenetic regulationEpigenetic epidemiologyEmbryonic developmentEpigenetic dysregulationGenetic lociEpigenetic reprogramingAssociation studiesMethylationRecent technical advancesEnvironmental factorsRegion analysisEpimutationsReprogramingEtiology of NDDIntellectual disabilityLociTechnical advancesAllelesRegulationInterferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance
Hlady RA, Zhao X, Khoury L, Luna A, Pham K, Wu Q, Lee J, Pyrsopoulos NT, Liu C, Robertson KD. Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance. Hepatology 2022, 75: 983-996. PMID: 34387871, PMCID: PMC9416882, DOI: 10.1002/hep.32111.Peer-Reviewed Original ResearchConceptsDNA methylationHistone modificationsWide DNA methylationAberrant DNA methylationGene expression analysisDNA methyltransferase inhibitorOpen chromatinEpigenetic mechanismsEpigenetic targetsHuman patient samplesEpigenetic changesEpigenomeMethyltransferase inhibitorTargetable vulnerabilitiesMethylationHCC cell linesImmortalized hepatocytesCell linesFunctional effectsChronic HCV infectionChromatinHCV infectionImmune responsePatient samplesSynergizesEpigenome-Wide Analysis Reveals DNA Methylation Alteration in ZFP57 and Its Target RASGFR2 in a Mexican Population Cohort with Autism
Aspra Q, Cabrera-Mendoza B, Morales-Marín ME, Márquez C, Chicalote C, Ballesteros A, Aguilar M, Castro X, Gómez-Cotero A, Balboa-Verduzco AM, Albores-Gallo L, Nafate-López O, Marcín-Salazar CA, Sánchez P, Lanzagorta-Piñol N, López-Armenta FO, Nicolini H. Epigenome-Wide Analysis Reveals DNA Methylation Alteration in ZFP57 and Its Target RASGFR2 in a Mexican Population Cohort with Autism. Children 2022, 9: 462. PMID: 35455506, PMCID: PMC9025761, DOI: 10.3390/children9040462.Peer-Reviewed Original ResearchDNA methylationGenome-wide differencesIllumina 450k arrayDNA methylation patternsDNA methylation profilesDNA methylation studiesDNA methylation alterationsWide analysisMethylation patternsEnvironmental factorsMethylation alterationsMethylation profilesMethylation studiesDifferent tissuesMethylationASD etiologyASD pathophysiologyComplex neurodevelopmental disorderMolecular alterationsEpithelium cellsNeurodevelopmental disordersComplex interactionsZFP57RasGRF2Diversity
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