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
2022
Taming the transposon: H3K9me3 turns foe to friend in human development
Chitrakar A, Noon M, Xiao AZ. Taming the transposon: H3K9me3 turns foe to friend in human development. Cell Stem Cell 2022, 29: 1009-1010. PMID: 35803220, PMCID: PMC9484580, DOI: 10.1016/j.stem.2022.06.010.Peer-Reviewed Original Research
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 structureRNA-based CRISPR-Mediated Loss-of-Function Mutagenesis in Human Pluripotent Stem Cells
Leung AW, Broton C, Bogacheva MS, Xiao AZ, Garcia-Castro MI, Lou YR. RNA-based CRISPR-Mediated Loss-of-Function Mutagenesis in Human Pluripotent Stem Cells. Journal Of Molecular Biology 2020, 432: 3956-3964. PMID: 32339532, DOI: 10.1016/j.jmb.2020.04.017.Peer-Reviewed Original ResearchConceptsHuman pluripotent stem cellsPluripotent stem cellsTargeting efficiencyShelf cell productsTransfection protocolShort palindromic repeatsStem cellsSelection markerGenome editingPS cell linesFunction mutagenesisImproved protocolBroad applicationsPalindromic repeatsClustered RegularlyAssociated 9Human therapyEfficiencyProtocolCell productsCRISPRCrRNARegularlyApplicationsEditing
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 modelGlioblastomaSilencingMapping and characterizing N6-methyladenine in eukaryotic genomes using single-molecule real-time sequencing
Zhu S, Beaulaurier J, Deikus G, Wu TP, Strahl M, Hao Z, Luo G, Gregory JA, Chess A, He C, Xiao A, Sebra R, Schadt EE, Fang G. Mapping and characterizing N6-methyladenine in eukaryotic genomes using single-molecule real-time sequencing. Genome Research 2018, 28: 1067-1078. PMID: 29764913, PMCID: PMC6028124, DOI: 10.1101/gr.231068.117.Peer-Reviewed Original ResearchConceptsSingle-molecule real-time sequencingEukaryotic genomesReal-time sequencingDAS eventsN6-methyladenineHuman lymphoblastoid cellsGenome-wide mapsSingle-nucleotide resolutionSingle-molecule resolutionLINE-1 elementsFull-length LINE-1 elementsGreen algaeProkaryotic genomesGenomeHigh-resolution mappingSequencing dataLymphoblastoid cellsSequencingEukaryotesProkaryotesMethylomeNovel formAlgaePromoterJoint analysis
2017
Quality control towards the application of induced pluripotent stem cells
Lin K, Xiao AZ. Quality control towards the application of induced pluripotent stem cells. Current Opinion In Genetics & Development 2017, 46: 164-169. PMID: 28823985, DOI: 10.1016/j.gde.2017.07.006.Peer-Reviewed Original Research
2015
Adaption 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 Research
2014
The 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 FactorsTrisomy
2009
Dephosphorylation of the C-terminal Tyrosyl Residue of the DNA Damage-related Histone H2A.X Is Mediated by the Protein Phosphatase Eyes Absent*
Krishnan N, Jeong DG, Jung SK, Ryu SE, Xiao A, Allis CD, Kim SJ, Tonks NK. Dephosphorylation of the C-terminal Tyrosyl Residue of the DNA Damage-related Histone H2A.X Is Mediated by the Protein Phosphatase Eyes Absent*. Journal Of Biological Chemistry 2009, 284: 16066-16070. PMID: 19351884, PMCID: PMC2713548, DOI: 10.1074/jbc.c900032200.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorDNA DamageDNA-Binding ProteinsElectrochemistryHistonesHumansIntracellular Signaling Peptides and ProteinsMetalsNuclear ProteinsPhosphorylationProtein Structure, TertiaryProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine PhosphatasesRNA InterferenceSubstrate SpecificityTransfectionTyrosineConceptsEyes AbsentDNA damage responseTyr-142Damage responseTyrosyl residuesProtein tyrosine phosphataseDNA damage repairAtypical kinaseHistone H2A.X.Haloacid dehalogenaseMammalian cellsHistone H2A.XDisplayed specificityElevated basal phosphorylationPhosphorylation statusRNA interferenceDamage repairPhysiological substratesH2A.XNovel roleBasal phosphorylationImportant regulatorDephosphorylationResiduesWSTF
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 roleMethylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity
Zhao X, Jankovic V, Gural A, Huang G, Pardanani A, Menendez S, Zhang J, Dunne R, Xiao A, Erdjument-Bromage H, Allis CD, Tempst P, Nimer SD. Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity. Genes & Development 2008, 22: 640-653. PMID: 18316480, PMCID: PMC2259033, DOI: 10.1101/gad.1632608.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CD34ArginineCell Line, TumorCore Binding Factor Alpha 2 SubunitDNA-Binding ProteinsGene Expression RegulationHematopoiesisHumansMethylationMutationPlatelet Membrane Glycoprotein IIbProtein-Arginine N-MethyltransferasesProto-Oncogene ProteinsRepressor ProteinsRNA, Small InterferingRUNX1 Translocation Partner 1 ProteinSin3 Histone Deacetylase and Corepressor ComplexTrans-ActivatorsTranscription FactorsTranscription, GeneticConceptsRUNX1 functionArginine residuesRUNX1-ETO fusion proteinArginine methyltransferase PRMT1Arginine methylation sitesPRMT1-dependent methylationRUNX1 target genesProtein-protein interactionsPost-translational modificationsRUNX1/AML1Dominant inhibitory activityDefinitive hematopoiesisMethyltransferase PRMT1Corepressor Sin3ATranscriptional coactivatorPRMT1Target genesMethylation sitesDynamic regulationTranscriptional activityCorepressor bindingHuman acute leukemiaFusion proteinChromosome translocationRUNX1
2004
Linking the epigenetic ‘language’ of covalent histone modifications to cancer
Hake SB, Xiao A, Allis CD. Linking the epigenetic ‘language’ of covalent histone modifications to cancer. British Journal Of Cancer 2004, 90: 761-769. PMID: 14970850, PMCID: PMC2410168, DOI: 10.1038/sj.bjc.6601575.Peer-Reviewed Original ResearchConceptsCovalent histone modificationsHistone modificationsMethylation of DNAChromatin reorganisationEpigenetic modulationCovalent modificationHuman biologyHuman cancersMultistep processMethylationRecent findingsChromatinHuman healthHistonesEpigeneticsPhosphorylationBiologyAcetylationDNAModificationPotential therapyCarcinogenesisMajor partCancer