2025
ETS emerges to heat up adipose
Rodeheffer M. ETS emerges to heat up adipose. Genes & Development 2025 PMID: 40389324, DOI: 10.1101/gad.352966.125.Peer-Reviewed Original ResearchTranscription factor bindingE26 transformation-specific (ETS) transcription factorsPromoter chromatin accessibilityChromatin accessibilityFactor bindingTranscription factorsHistone acetylationAdipose biologyGene expressionETV4HistoneTranscriptionGenesUCP1AcetylationE26AdipogenesisBindingBiologyThermogenesisExpressionAdiposeNutrient-driven histone code determines exhausted CD8+ T cell fates
Ma S, Dahabieh M, Mann T, Zhao S, McDonald B, Song W, Chung H, Farsakoglu Y, Garcia-Rivera L, Hoffmann F, Xu S, Du V, Chen D, Furgiuele J, LaPorta M, Jacobs E, DeCamp L, Oswald B, Sheldon R, Ellis A, Liu L, He P, Wang Y, Jang C, Jones R, Kaech S. Nutrient-driven histone code determines exhausted CD8+ T cell fates. Science 2025, 387: eadj3020. PMID: 39666821, PMCID: PMC11881194, DOI: 10.1126/science.adj3020.Peer-Reviewed Original ResearchATP-citrate lyaseAcetyl-CoA synthetase 2Histone codeCD8<sup>+</sup> T cell differentiationTumor-specific T-cell responsesACLY inhibitionHistone acetylationCD8+ T cell fateExhausted T cellsT-cell therapyChronic viral infectionsT cell responsesT cell differentiationT cell fateT cell genesTex cellsT cellsEpigenetic modificationsEpigenetic remodelingViral infectionCitrate metabolismNutrient metabolismHistoneAcetylationDifferentiation
2024
ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses
Kaymak I, Watson M, Oswald B, Ma S, Johnson B, DeCamp L, Mabvakure B, Luda K, H. E, Lau K, Fu Z, Muhire B, Kitchen-Goosen S, Vander Ark A, Dahabieh M, Samborska B, Vos M, Shen H, Fan Z, Roddy T, Kingsbury G, Sousa C, Krawczyk C, Williams K, Sheldon R, Kaech S, Roy D, Jones R. ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses. Journal Of Experimental Medicine 2024, 221: e20231820. PMID: 39150482, PMCID: PMC11329787, DOI: 10.1084/jem.20231820.Peer-Reviewed Original ResearchConceptsAcyl-CoA synthetase short-chain family member 2Acetyl-CoA productionATP citrate lyaseChromatin accessibilityAcetyl-CoAEnzyme ATP citrate lyaseFamily member 2Function in vivoCoordination of cellular metabolismTCA cycleMetabolic nodesGene locusCitrate lyaseT cell effector responsesHistone acetylationCellular metabolismEffector functionsCD8 T cellsResponse to infectionMember 2ChromatinEffector responsesMetabolic substratesT cell response to infectionT cells
2023
TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes
Boutagy N, Fowler J, Grabinska K, Cardone R, Sun Q, Vazquez K, Whalen M, Zhu X, Chakraborty R, Martin K, Simons M, Romanoski C, Kibbey R, Sessa W. TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2218150120. PMID: 37695914, PMCID: PMC10515159, DOI: 10.1073/pnas.2218150120.Peer-Reviewed Original ResearchConceptsPyruvate dehydrogenase kinase 4Dehydrogenase kinase 4Lon proteasePyruvate dehydrogenase activityHistone acetylationMitochondrial metabolismKinase 4Specific gene lociPDH fluxEndothelial cellsSiRNA-mediated knockdownAcetyl-CoA generationLysine 27Gene transcriptionTCA fluxRNA sequencingHuman umbilical vein endothelial cellsProtein degradationHistone 3Gene locusUmbilical vein endothelial cellsNF-κB-dependent mechanismTricarboxylic acid cycle fluxVein endothelial cellsActive subunit
2022
Plant-specific HDT family histone deacetylases are nucleoplasmins
Bobde R, Kumar A, Vasudevan D. Plant-specific HDT family histone deacetylases are nucleoplasmins. The Plant Cell 2022, 34: 4760-4777. PMID: 36069647, PMCID: PMC9709999, DOI: 10.1093/plcell/koac275.Peer-Reviewed Original ResearchConceptsN-terminal domainHistone chaperonesH2A/H2B dimersHistones H3/H4H3/H4Nucleosome dynamicsH2B dimersSequence similarityHistone acetyltransferaseEnigmatic familyHistone acetylationFunctional characterizationNucleoplasminGene expressionHistone deacetylasesC-terminalHistone deacetylaseUrea conditionsHistone oligomersSolution structureChaperonesDifferent familiesArabidopsisA serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility
Sheu SH, Upadhyayula S, Dupuy V, Pang S, Deng F, Wan J, Walpita D, Pasolli HA, Houser J, Sanchez-Martinez S, Brauchi SE, Banala S, Freeman M, Xu CS, Kirchhausen T, Hess HF, Lavis L, Li Y, Chaumont-Dubel S, Clapham DE. A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility. Cell 2022, 185: 3390-3407.e18. PMID: 36055200, PMCID: PMC9789380, DOI: 10.1016/j.cell.2022.07.026.Peer-Reviewed Original ResearchConceptsCA1 pyramidal neuronsChromatin accessibilityPyramidal neuronsSerotonergic axonsEpigenetic statePrimary ciliaHippocampal CA1 pyramidal neuronsChemogenetic stimulationSerotonin receptorsNuclear actinReceptor 6Histone acetylationAxonsChemical synapsesIntercellular communicationRhoA pathwaySynapseNeuronsCiliaSynapsesStimulationPathwayNeurotransmissionReceptorsHistone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity
Chakraborty R, Ostriker AC, Xie Y, Dave JM, Gamez-Mendez A, Chatterjee P, Abu Y, Valentine J, Lezon-Geyda K, Greif DM, Schulz VP, Gallagher PG, Sessa WC, Hwa J, Martin KA. Histone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity. Circulation 2022, 145: 1720-1737. PMID: 35502657, PMCID: PMC12047542, DOI: 10.1161/circulationaha.121.057599.Peer-Reviewed Original ResearchConceptsHistone acetylationContractile genesContractile protein expressionPhenotypic switchingHistone acetyl transferase p300Human intimal hyperplasiaPlatelet-derived growth factor treatmentAcetyl transferase p300Key regulatory mechanismSmooth muscle cell phenotypeP300 expressionP300-dependent acetylationSmooth muscle plasticityDistinct functional interactionsMuscle cell phenotypeProtein expressionIntimal hyperplasiaRole of p300Methylcytosine dioxygenase TET2Chromatin modificationsEpigenetic regulationVSMC phenotypic switchingSpecific histoneCardiovascular diseaseMaster regulatorChromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia
Farrelly L, Zheng S, Schrode N, Topol A, Bhanu N, Bastle R, Ramakrishnan A, Chan J, Cetin B, Flaherty E, Shen L, Gleason K, Tamminga C, Garcia B, Li H, Brennand K, Maze I. Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia. Nature Communications 2022, 13: 2195. PMID: 35459277, PMCID: PMC9033776, DOI: 10.1038/s41467-022-29922-0.Peer-Reviewed Original ResearchConceptsHistone posttranslational modificationsPosttranslational modificationsUnbiased proteomic approachPluripotent stem cellsPatient-derived neuronsH2A.Z acetylationChromatin profilingHyperacetylated histonesFamily proteinsProteomic approachProtein interactionsHistone acetylationTranscriptional abnormalitiesEpigenetic factorsExtraterminal (BET) proteinsSZ casesRisk variantsHuman neuronsStem cellsAberrant roleProtein inhibitionBona fideTreatment of schizophreniaPostmortem human brainCritical roleMechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo
Greuter T, Yaqoob U, Gan C, Jalan-Sakrikar N, Kostallari E, Lu J, Gao J, Sun L, Liu M, Sehrawat TS, Ibrahim SH, Furuta K, Nozickova K, Huang BQ, Gao B, Simons M, Cao S, Shah VH. Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo. Journal Of Hepatology 2022, 77: 723-734. PMID: 35421427, PMCID: PMC9391258, DOI: 10.1016/j.jhep.2022.03.029.Peer-Reviewed Original ResearchConceptsFocal adhesionsGlycolytic enzymesIsolated focal adhesionsChromosome conformation captureHistone activation marksChromatin immunoprecipitation analysisConformation captureChIP sequencingActivation marksEpigenetic regulationActin dynamicsHistone acetylationRNA sequencingERT2 miceActin polymerizationEndothelial cellsCXCL1 promoterNovel roleIntegrin β1Druggable targetsInhibition of glycolysisNuclear chromatinGlycolysisAngiocrineEnzyme
2021
mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism.
Collins S, Oh M, Sun I, Chan-Li Y, Zhao L, Powell J, Horton M. mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism. The Journal Of Immunology 2021, 207: 913-922. PMID: 34290107, DOI: 10.4049/jimmunol.2100230.Peer-Reviewed Original ResearchConceptsKey regulatorImmune cell functionEnhanced histone acetylationCell functionRapid energy sourceClass III histoneDifferentiation of macrophagesHistone acetylationMacrophage functionMTORC1 signalingCellular metabolismOxidative phosphorylationCell metabolismMTOR signalingGlycolytic metabolismAntimicrobial compoundsGenetic deletionM2 macrophagesMouse macrophagesProper wound healingMetabolic programmingSignificant defectsM1 functionImmune cell metabolismSignalingH3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation
Dong J, LeBlanc C, Poulet A, Mermaz B, Villarino G, Webb KM, Joly V, Mendez J, Voigt P, Jacob Y. H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation. The Plant Cell 2021, 33: 961-979. PMID: 33793815, PMCID: PMC8226292, DOI: 10.1093/plcell/koaa027.Peer-Reviewed Original ResearchConceptsGenome stabilityGenomic instabilityHistone acetylationSAGA-like complexesMultiple lysine residuesArabidopsis GCN5ARABIDOPSIS TRITHORAXArabidopsis thalianaTranscriptional silencingHeterochromatin defectsDouble mutantDNA replicationEpigenetic mechanismsGCN5Molecular roleEssential functionsDiverse rolesMolecular mechanismsLysine residuesProtein 5AcetylationMutantsPlantsADA2bATXR6
2019
Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses
Langston PK, Nambu A, Jung J, Shibata M, Aksoylar HI, Lei J, Xu P, Doan MT, Jiang H, MacArthur MR, Gao X, Kong Y, Chouchani ET, Locasale JW, Snyder NW, Horng T. Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses. Nature Immunology 2019, 20: 1186-1195. PMID: 31384058, PMCID: PMC6707851, DOI: 10.1038/s41590-019-0453-7.Peer-Reviewed Original ResearchConceptsAcetyl coenzyme AGlycerol phosphate shuttleInduction of genesCoenzyme APhosphate shuttleAcetylation of histonesHistone acetylationInflammatory responseMitochondrial glycerolGPD2Inflammatory mediatorsMicrobial infectionsMicrobial stimulationGenesHost defenseGlucose oxidationAcetylationOxidative metabolismBacterial lipopolysaccharideSustained inflammationMacrophage activationHistonesDetrimental effectsMacrophagesAcute exposureDistinct modes of mitochondrial metabolism uncouple T cell differentiation and function
Bailis W, Shyer JA, Zhao J, Canaveras JCG, Al Khazal FJ, Qu R, Steach HR, Bielecki P, Khan O, Jackson R, Kluger Y, Maher LJ, Rabinowitz J, Craft J, Flavell RA. Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function. Nature 2019, 571: 403-407. PMID: 31217581, PMCID: PMC6939459, DOI: 10.1038/s41586-019-1311-3.Peer-Reviewed Original ResearchConceptsMitochondrial citrate exportTerminal effector functionsMalate-aspartate shuttleCitrate exportHistone acetylationCell differentiationComplex ICellular biochemical compositionT cell differentiationSuccinate dehydrogenaseT cell activationExpression of genesElectron transport chainTricarboxylic acid cycleT cell receptor ligationAnabolic programTranscriptional remodellingTranscriptional programmingEpigenetic remodellingSignal transductionCell activationMetabolic reprogrammingCell statesDistinct modesEffector functionsBrd4 and P300 Confer Transcriptional Competency during Zygotic Genome Activation
Chan SH, Tang Y, Miao L, Darwich-Codore H, Vejnar CE, Beaudoin JD, Musaev D, Fernandez JP, Benitez MDJ, Bazzini AA, Moreno-Mateos MA, Giraldez AJ. Brd4 and P300 Confer Transcriptional Competency during Zygotic Genome Activation. Developmental Cell 2019, 49: 867-881.e8. PMID: 31211993, PMCID: PMC7201981, DOI: 10.1016/j.devcel.2019.05.037.Peer-Reviewed Original ResearchConceptsGenome activationTranscriptional competencyHistone acetylationP300-dependent histone acetylationZygotic genome activationFirst zygotic genesMaternal mRNA translationZygotic genesAnimal developmentZygotic developmentDevelopmental reprogrammingMRNA translationLive imagingCell cycleSilent genomeBRD4ZebrafishGenomeTranscriptionAcetylationActivationP300FertilizationReprogrammingGenes
2017
Coordinating Regulation of Gene Expression in Cardiovascular Disease: Interactions between Chromatin Modifiers and Transcription Factors
Bauer AJ, Martin KA. Coordinating Regulation of Gene Expression in Cardiovascular Disease: Interactions between Chromatin Modifiers and Transcription Factors. Frontiers In Cardiovascular Medicine 2017, 4: 19. PMID: 28428957, PMCID: PMC5382160, DOI: 10.3389/fcvm.2017.00019.Peer-Reviewed Original ResearchChromatin modifiersTranscription factorsGene expressionTranscriptional controlChromatin-modifying proteinsTranscription factor recruitmentDysregulated gene expressionNumerous cell typesChromatin structureFactor recruitmentHistone methylationGene accessibilityTranscriptional interactionsDNA methylationEpigenetic modifiersRegulatory regionsHistone acetylationVascular smooth muscle cellsCell typesSmooth muscle cellsMuscle cellsMethylationNovel therapeuticsExpressionDisease pathogenesisSystematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression
Fiziev P, Akdemir K, Miller J, Keung E, Samant N, Sharma S, Natale C, Terranova C, Maitituoheti M, Amin S, Martinez-Ledesma E, Dhamdhere M, Axelrad J, Shah A, Cheng C, Mahadeshwar H, Seth S, Barton M, Protopopov A, Tsai K, Davies M, Garcia B, Amit I, Chin L, Ernst J, Rai K. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression. Cell Reports 2017, 19: 875-889. PMID: 28445736, PMCID: PMC5473172, DOI: 10.1016/j.celrep.2017.03.078.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationCell LineCell ProliferationChromatinChromatin ImmunoprecipitationDisease-Free SurvivalEpigenomicsHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHumansHydroxamic AcidsKaplan-Meier EstimateMelanomaPrincipal Component AnalysisPTEN PhosphohydrolaseRNA InterferenceRNA, Small InterferingSignal TransductionVorinostatConceptsChromatin state transitionsMelanoma progressionChromatin state changesGene expression patternsCancer regulatory genesChromatin stateEpigenomic profilingEpigenomic changesEpigenomic analysisTumorigenic stateEpigenetic modificationsTranscriptomic analysisRegulatory regionsHistone acetylationAcetylation changesHistone deacetylase inhibitorsExpression patternsHyperproliferative phenotypeAcetylation levelsTumorigenic cellsHuman melanoma cellsFunctional rolePhenotypic modelDeacetylase inhibitorsMelanoma cells
2015
Roles for Histone Acetylation in Regulation of Telomere Elongation and Two‐cell State in Mouse ES Cells
Dan J, Yang J, Liu Y, Xiao A, Liu L. Roles for Histone Acetylation in Regulation of Telomere Elongation and Two‐cell State in Mouse ES Cells. Journal Of Cellular Physiology 2015, 230: 2337-2344. PMID: 25752831, PMCID: PMC4711819, DOI: 10.1002/jcp.24980.Peer-Reviewed Original ResearchConceptsHistone acetylation levelsES cellsHistone acetylationHistone hypoacetylationHistone hyperacetylationTelomere elongationAcetylation levelsWild-type ES cellsRepressive DNA methylationRepressive epigenetic marksTelomere length maintenanceTwo-cell stateMouse ES cellsMammalian telomeresHeterochromatic stateEpigenetic marksHistone methylationLength maintenanceEpigenetic modificationsDNA methylationTelomere recombinationHistone deacetylase inhibitorsSpecific genesGene expressionTelomeres
2014
Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma
Kailasam A, Mittal S, Agrawal D. Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma. Clinical And Translational Science 2014, 8: 394-402. PMID: 25388215, PMCID: PMC4429045, DOI: 10.1111/cts.12242.Peer-Reviewed Original ResearchConceptsHistone acetylationBarrett's esophagus to esophageal adenocarcinomaEsophageal adenocarcinomaCell cycle controlBase pair sequenceDNA base pair sequencesWnt-related genesBarrett's esophagusDNA methylationProapoptotic genesEpigenetic profilesCycle controlPathogenesis of esophageal adenocarcinomaGenetic makeupEpigenetic changesDevelopment of esophageal adenocarcinomaTumor suppressorGenesDevelopment of Barrett's esophagusDown-regulationEpigenetic influencesHistoneTreatment to patientsDNAPremalignant conditionGenetic and epigenetic fine mapping of causal autoimmune disease variants
Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, Shoresh N, Whitton H, Ryan RJ, Shishkin AA, Hatan M, Carrasco-Alfonso MJ, Mayer D, Luckey CJ, Patsopoulos NA, De Jager PL, Kuchroo VK, Epstein CB, Daly MJ, Hafler DA, Bernstein BE. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 2014, 518: 337-343. PMID: 25363779, PMCID: PMC4336207, DOI: 10.1038/nature13835.Peer-Reviewed Original ResearchConceptsCausal variantsAutoimmune diseasesT cellsRegulatory T cellsNon-coding risk variantsT cell subsetsEnhancer-associated RNAsGenome-wide association studiesPrimary immune cellsCandidate causal variantsGene regulatory modelsImmune cellsImmune stimulationB cellsGene activationFine mappingTranscription factorsMaster regulatorHistone acetylationImmune differentiationSequence determinantsGene expressionAssociation studiesDiseaseHuman diseasesRepeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex
Park H, Yu H, Park S, Ahn Y, Kim Y, Kim H. Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex. The International Journal Of Neuropsychopharmacology 2014, 17: 1487-1500. PMID: 24606669, DOI: 10.1017/s1461145714000248.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnalysis of VarianceAnimalsButyric AcidChromatin ImmunoprecipitationDisease Models, AnimalElectroshockFrontal LobeGene Expression RegulationGlial Fibrillary Acidic ProteinHistamine AntagonistsHistone Deacetylase 2MalePhosphopyruvate HydrataseRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateRNA, MessengerSeizuresSignal TransductionConceptsSignaling-related genesHistone deacetylasesHistone modificationsHistone acetylationCalcium/calmodulin-dependent protein kinase II alphaChromatin immunoprecipitation analysisRat frontal cortexEarly growth response 1Transcriptional repressionReceptor-related genesHistone deacetylationH4 proteinN-methyl-D-aspartate 2ATarget genesFrontal cortexImmunoprecipitation analysisElectroconvulsive seizuresGene expressionResponse 1GenesHDAC2 expressionNeuronal cellsECS treatmentClass I HDACsII alpha
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