2023
ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m6A modification-mediated RNA stability control
Gao Y, Zimmer J, Vasic R, Liu C, Gbyli R, Zheng S, Patel A, Liu W, Qi Z, Li Y, Nelakanti R, Song Y, Biancon G, Xiao A, Slavoff S, Kibbey R, Flavell R, Simon M, Tebaldi T, Li H, Halene S. ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m6A modification-mediated RNA stability control. Cell Reports 2023, 42: 113163. PMID: 37742191, PMCID: PMC10636609, DOI: 10.1016/j.celrep.2023.113163.Peer-Reviewed Original ResearchConceptsAlkB homolog 5Post-transcriptional regulatory mechanismsHematopoietic stemNumerous cellular processesProgenitor cell fitnessEnergy metabolismMitochondrial ATP productionMethyladenosine (m<sup>6</sup>A) RNA modificationTricarboxylic acid cycleCell energy metabolismHuman hematopoietic cellsMitochondrial energy productionCell fitnessCellular processesRNA modificationsRNA methylationRegulatory mechanismsEnzyme transcriptsATP productionHomolog 5Acid cycleΑ-ketoglutarateHematopoietic cellsMessenger RNAΑ-KGMammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
de Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, PMCID: PMC10957226, DOI: 10.1016/j.ccell.2023.07.005.Peer-Reviewed Original ResearchConceptsMammalian SWI/SNF chromatinSWI/SNF chromatinMSWI/SNF complexesGenome-wide localizationGene regulatory signaturesNon-genetic mechanismsEpithelial cell differentiationEGFR-mutant cellsChromatin accessibilitySNF complexCellular programsRegulatory signaturesTKI-resistant lung cancerGene targetsKinase inhibitor resistanceCell differentiationMesenchymal transitionTKI resistancePharmacologic disruptionTyrosine kinase inhibitor resistanceCell proliferationChromatinInhibitor resistanceEGFR-mutant lungKinase inhibitors
2020
A New Link to Primate Heart Development
Nelakanti RV, Xiao AZ. A New Link to Primate Heart Development. Developmental Cell 2020, 54: 685-686. PMID: 32991832, DOI: 10.1016/j.devcel.2020.09.009.Commentaries, Editorials and LettersN6-methyladenine in DNA antagonizes SATB1 in early development
Li Z, Zhao S, Nelakanti RV, Lin K, Wu TP, Alderman MH, Guo C, Wang P, Zhang M, Min W, Jiang Z, Wang Y, Li H, Xiao AZ. N6-methyladenine in DNA antagonizes SATB1 in early development. Nature 2020, 583: 625-630. PMID: 32669713, PMCID: PMC8596487, DOI: 10.1038/s41586-020-2500-9.Peer-Reviewed Original ResearchConceptsN6-mAN6-methyladenineMouse trophoblast stem cellsLarge chromatin domainsCell fate transitionsLarge-scale chromatinUnexpected molecular mechanismTrophoblast stem cellsEarly embryonic developmentDNA secondary structuresEarly developmentFate transitionsMammalian genomesChromatin domainsEpigenetic landscapeGene regulationChromatin organizerEmbryonic developmentDNA modificationsBiological roleMolecular mechanismsSATB1 functionsMolecular pathwaysCell culture modelSecondary structurem6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development
Gao Y, Vasic R, Song Y, Teng R, Liu C, Gbyli R, Biancon G, Nelakanti R, Lobben K, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA, Li HB, Tebaldi T, Halene S. m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development. Immunity 2020, 52: 1007-1021.e8. PMID: 32497523, PMCID: PMC7408742, DOI: 10.1016/j.immuni.2020.05.003.Peer-Reviewed Original ResearchConceptsDouble-stranded RNADeleterious innate immune responseMammalian hematopoietic developmentEndogenous double-stranded RNAHematopoietic developmentInnate immune responseAbundant RNA modificationMurine fetal liverPattern recognition receptor pathwaysImmune responseProtein codingDsRNA formationRNA modificationsWriter METTL3Hematopoietic defectsPerinatal lethalityNative stateConditional deletionAberrant innate immune responsesLoss of METTL3Hematopoietic failureReceptor pathwayAberrant immune responsePrevents formationFetal liverMammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA
Zhang M, Yang S, Nelakanti R, Zhao W, Liu G, Li Z, Liu X, Wu T, Xiao A, Li H. Mammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA. Cell Research 2020, 30: 197-210. PMID: 32051560, PMCID: PMC7054317, DOI: 10.1038/s41422-019-0237-5.Peer-Reviewed Original ResearchConceptsN6-mAMammalian genomesStructure-based mutagenesis studiesBase unpairing regionsChromosome regulationDNA demethylasesStructural studiesEpigenetic marksDNA demethylaseMouse genomeEarly embryogenesisGenomic studiesBase flippingN6-methyladenineALKBH1Mutagenesis studiesFlipped baseGenomeProfiling studiesDNACatalytic centerDemethylaseActive regulationRegulationDemethylases
2019
N(6)-Methyladenine in eukaryotes
Alderman MH, Xiao AZ. N(6)-Methyladenine in eukaryotes. Cellular And Molecular Life Sciences 2019, 76: 2957-2966. PMID: 31143960, PMCID: PMC6857450, DOI: 10.1007/s00018-019-03146-w.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2018
N 6 -methyladenine DNA Modification in Glioblastoma
Xie Q, Wu TP, Gimple RC, Li Z, Prager BC, Wu Q, Yu Y, Wang P, Wang Y, Gorkin DU, Zhang C, Dowiak AV, Lin K, Zeng C, Sui Y, Kim LJY, Miller TE, Jiang L, Lee-Poturalski C, Huang Z, Fang X, Zhai K, Mack SC, Sander M, Bao S, Kerstetter-Fogle AE, Sloan AE, Xiao AZ, Rich JN. N 6 -methyladenine DNA Modification in Glioblastoma. Cell 2018, 175: 1228-1243.e20. PMID: 30392959, PMCID: PMC6433469, DOI: 10.1016/j.cell.2018.10.006.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAdultAgedAlkB Homolog 1, Histone H2a DioxygenaseAnimalsAstrocytesBrain NeoplasmsCell HypoxiaChildDNA MethylationEpigenomicsFemaleGlioblastomaHeterochromatinHistonesHumansKaplan-Meier EstimateMaleMiceMiddle AgedNeoplastic Stem CellsRNA InterferenceRNA, Small InterferingTumor Suppressor Protein p53ConceptsDNA modificationsHeterochromatic histone modificationsRegulation of transcriptionNovel DNA modificationChromatin accessibilityEpigenetic marksHistone modificationsTranscriptional silencingEpigenetic modificationsGenetic driversHuman diseasesOncogenic pathwaysTumor cell proliferationPotential therapeutic targetALKBH1Cell proliferationTumor-bearing miceCritical roleTherapeutic targetDNAHuman tissuesHuman glioblastoma modelGlioblastoma modelGlioblastomaSilencing
2017
Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells
Choi J, Huebner AJ, Clement K, Walsh RM, Savol A, Lin K, Gu H, Di Stefano B, Brumbaugh J, Kim SY, Sharif J, Rose CM, Mohammad A, Odajima J, Charron J, Shioda T, Gnirke A, Gygi S, Koseki H, Sadreyev RI, Xiao A, Meissner A, Hochedlinger K. Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells. Nature 2017, 548: 219-223. PMID: 28746311, PMCID: PMC5905676, DOI: 10.1038/nature23274.Peer-Reviewed Original Research
2016
DNA methylation on N6-adenine in mammalian embryonic stem cells
Wu TP, Wang T, Seetin MG, Lai Y, Zhu S, Lin K, Liu Y, Byrum SD, Mackintosh SG, Zhong M, Tackett A, Wang G, Hon LS, Fang G, Swenberg JA, Xiao AZ. DNA methylation on N6-adenine in mammalian embryonic stem cells. Nature 2016, 532: 329-333. PMID: 27027282, PMCID: PMC4977844, DOI: 10.1038/nature17640.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAlkB Homolog 1, Histone H2a DioxygenaseAnimalsCell DifferentiationDNA MethylationDNA Transposable ElementsDNA-(Apurinic or Apyrimidinic Site) LyaseEnhancer Elements, GeneticEpigenesis, GeneticEvolution, MolecularGene SilencingLong Interspersed Nucleotide ElementsMammalsMiceMouse Embryonic Stem CellsUp-RegulationX ChromosomeConceptsLINE-1 transposonsEmbryonic stem cellsN6-methyladenineMammalian genomesEpigenetic silencingDNA methylationX chromosomeMammalian embryonic stem cellsEmbryonic stem cell differentiationMouse embryonic stem cellsStem cellsStem cell differentiationMammalian evolutionTranscriptional silencingEvolutionary ageGene activationDNA modificationsL1 elementsCell differentiationSilencingTransposonN6-adenineGenomeActivation signalsChromosomes
2015
Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells
Benchetrit H, Herman S, van Wietmarschen N, Wu T, Makedonski K, Maoz N, Tov N, Stave D, Lasry R, Zayat V, Xiao A, Lansdorp PM, Sebban S, Buganim Y. Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells. Cell Stem Cell 2015, 17: 543-556. PMID: 26412562, DOI: 10.1016/j.stem.2015.08.006.Peer-Reviewed Original ResearchConceptsNuclear reprogrammingEmbryonic stem cellsStem-like cellsTransient pluripotent stateStem cellsDNA methylation profilesPluripotent stem cellsPluripotent stateLineage conversionTranscriptional profilesTransient expressionMethylation profilesReprogrammingEvidence of passageMouse fibroblastsPluripotencyChimera assaysLineagesCellsHigh degreeTranscriptomeTFAP2CMethylationDifferentiationEomesAdaption by Rewiring Epigenetic Landscapes
Liu Y, Xiao A. Adaption by Rewiring Epigenetic Landscapes. Cell Stem Cell 2015, 17: 249-250. PMID: 26340521, PMCID: PMC4710369, DOI: 10.1016/j.stem.2015.08.015.Peer-Reviewed Original ResearchRoles 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
Histone Variant H2A.X Deposition Pattern Serves as a Functional Epigenetic Mark for Distinguishing the Developmental Potentials of iPSCs
Wu T, Liu Y, Wen D, Tseng Z, Tahmasian M, Zhong M, Rafii S, Stadtfeld M, Hochedlinger K, Xiao A. Histone Variant H2A.X Deposition Pattern Serves as a Functional Epigenetic Mark for Distinguishing the Developmental Potentials of iPSCs. Cell Stem Cell 2014, 15: 281-294. PMID: 25192463, DOI: 10.1016/j.stem.2014.06.004.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsLineage gene expressionHistone variant H2A.XCell lineage commitmentDevelopmental potentialMouse iPSC linesIPSC linesPluripotent stem cell (iPSC) technologyEpigenetic marksLineage genesEpigenetic mechanismsLineage commitmentLineage differentiationExtraembryonic differentiationStem cell technologyGene expressionTetraploid complementationIPSC clonesIPSC qualityStem cellsFunctional markersH2A.XDifferentiationIPSCsComplementationThe Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection
Buganim Y, Markoulaki S, van Wietmarschen N, Hoke H, Wu T, Ganz K, Akhtar-Zaidi B, He Y, Abraham BJ, Porubsky D, Kulenkampff E, Faddah DA, Shi L, Gao Q, Sarkar S, Cohen M, Goldmann J, Nery JR, Schultz MD, Ecker JR, Xiao A, Young RA, Lansdorp PM, Jaenisch R. The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection. Cell Stem Cell 2014, 15: 295-309. PMID: 25192464, PMCID: PMC4170792, DOI: 10.1016/j.stem.2014.07.003.Peer-Reviewed Original ResearchAnimalsCell LineCellular ReprogrammingChimeraChromosomes, Human, Pair 8DNA MethylationEmbryonic Stem CellsEnhancer Elements, GeneticGene Expression ProfilingGenomeHistonesHumansInduced Pluripotent Stem CellsKruppel-Like Factor 4Mice, Inbred C57BLMice, Inbred DBARNA, MessengerTranscription FactorsTrisomyUsing Native Chromatin Immunoprecipitation to Interrogate Histone Variant Protein Deposition in Embryonic Stem Cells
Tseng Z, Wu T, Liu Y, Zhong M, Xiao A. Using Native Chromatin Immunoprecipitation to Interrogate Histone Variant Protein Deposition in Embryonic Stem Cells. Methods In Molecular Biology 2014, 1176: 11-22. PMID: 25030915, DOI: 10.1007/978-1-4939-0992-6_2.Peer-Reviewed Original ResearchConceptsNative chromatin immunoprecipitationHigh-throughput sequencingEmbryonic stem cellsChromatin immunoprecipitationHistone variantsMouse embryonic stem cellsGenome-wide localizationChromatin-associated factorsStem cellsProtein of interestMassive parallel sequencingHistone modificationsChromatin regionsChromatin pelletEpigenetic techniquesDNA fragmentsParallel sequencingImmunoprecipitationLibrary constructionSequencingEnzymatic digestionProtein depositionCellsH2A.XSpecific antibodiesRif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing
Dan J, Liu Y, Liu N, Chiourea M, Okuka M, Wu T, Ye X, Mou C, Wang L, Wang L, Yin Y, Yuan J, Zuo B, Wang F, Li Z, Pan X, Yin Z, Chen L, Keefe DL, Gagos S, Xiao A, Liu L. Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing. Developmental Cell 2014, 29: 7-19. PMID: 24735877, PMCID: PMC4720134, DOI: 10.1016/j.devcel.2014.03.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEmbryonic Stem CellsGene DeletionGene Expression Regulation, DevelopmentalGene SilencingHeterochromatinHistonesMethylationMiceProtein BindingProtein Processing, Post-TranslationalRecombination, GeneticRNA, MessengerTelomereTelomere HomeostasisTelomere-Binding ProteinsTranscription FactorsConceptsTelomere length homeostasisEmbryonic stem cellsLength homeostasisZscan4 expressionHeterochromatic silencingHeterochromatin silencingMethylation complexChromosomal fusionsEmbryonic lethalityGenomic stabilityTelomere elongationH3K9me3 levelsSubtelomeric regionsRecombination defectsLength heterogeneityStem cellsRIF1HomeostasisSilencingExpressionZscan4HyperrecombinationShRNALethalityInteracts
2009
A distinct H2A.X isoform is enriched in Xenopus laevis eggs and early embryos and is phosphorylated in the absence of a checkpoint
Shechter D, Chitta RK, Xiao A, Shabanowitz J, Hunt DF, Allis CD. A distinct H2A.X isoform is enriched in Xenopus laevis eggs and early embryos and is phosphorylated in the absence of a checkpoint. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 749-754. PMID: 19131518, PMCID: PMC2630098, DOI: 10.1073/pnas.0812207106.Peer-Reviewed Original ResearchConceptsDNA damageEarly embryosSignificance of phosphorylationTerminal consensus sequenceExogenous DNA damageDNA damage responseCell-free egg extractsPhospho-specific antibodiesEarly cell cyclesFrog Xenopus laevisMulticellular organismsH2A variantsXenopus tropicalisDamage responseUnannotated isoformsMammalian cellsHistone H2A.XSomatic cellsCheckpoint conditionsXenopus laevis eggsAquatic speciesEgg extractsConsensus sequenceCell cycleH2A.X
2008
WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity
Xiao A, Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, Ishibe-Murakami S, Wang B, Tempst P, Hofmann K, Patel DJ, Elledge SJ, Allis CD. WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature 2008, 457: 57-62. PMID: 19092802, PMCID: PMC2854499, DOI: 10.1038/nature07668.Peer-Reviewed Original ResearchConceptsDNA damage responseIntrinsic tyrosine kinase activityTyrosine kinase activityDamage responseKinase activityWilliams-Beuren syndrome transcription factorDouble-strand break responseNew regulatory mechanismWICH complexKinase foldEukaryotic cellsTranscription factorsWSTFKnowledge of domainsGenomic instabilityBreak responseSequence homologyRegulatory mechanismsCell deathPrecise rolePhosphorylationRepair processNew mechanismChromatinImportant role