Featured Publications
Acetyl-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 signalsHistonesBRD2Enhanced nucleotide chemistry and toehold nanotechnology reveals lncRNA spreading on chromatin
Machyna M, Kiefer L, Simon MD. Enhanced nucleotide chemistry and toehold nanotechnology reveals lncRNA spreading on chromatin. Nature Structural & Molecular Biology 2020, 27: 297-304. PMID: 32157249, DOI: 10.1038/s41594-020-0390-z.Peer-Reviewed Original ResearchConceptsHybridization capture approachGenome-wide changesLong non-coding RNAsUnfolded protein responseNon-coding RNAsStrand exchange reactionLncRNA localizationIndividual RNAsRNA captureUncharacterized changesX chromosomeProtein responseHeat shockChromatinLncRNAsRNACapture approachBinding sitesNucleic acidsNucleotide chemistryRoX2AutosomesChromosomesRelocalizationSpeciesHigh-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation
Simon MD, Pinter SF, Fang R, Sarma K, Rutenberg-Schoenberg M, Bowman SK, Kesner BA, Maier VK, Kingston RE, Lee JT. High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature 2013, 504: 465-469. PMID: 24162848, PMCID: PMC3904790, DOI: 10.1038/nature12719.Peer-Reviewed Original Research
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-KG
2021
Noncoding RNAs: biology and applications—a Keystone Symposia report
Cable J, Heard E, Hirose T, Prasanth KV, Chen L, Henninger JE, Quinodoz SA, Spector DL, Diermeier SD, Porman AM, Kumar D, Feinberg MW, Shen X, Unfried JP, Johnson R, Chen C, Wilusz JE, Lempradl A, McGeary SE, Wahba L, Pyle AM, Hargrove AE, Simon MD, Marcia M, Przanowska RK, Chang HY, Jaffrey SR, Contreras LM, Chen Q, Shi J, Mendell JT, He L, Song E, Rinn JL, Lalwani MK, Kalem MC, Chuong EB, Maquat LE, Liu X. Noncoding RNAs: biology and applications—a Keystone Symposia report. Annals Of The New York Academy Of Sciences 2021, 1506: 118-141. PMID: 34791665, PMCID: PMC9808899, DOI: 10.1111/nyas.14713.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsKeystone Symposia reportPotential drug targetsRNA biologyHuman transcriptomeEpigenetic modificationsKeystone eSymposiumNoncoding RNAsCell signalingBasic biologyDrug targetsRNABiologyDisease mechanismsNucleotidesSpeciesTranscriptomeImportant roleRNAsTranscriptionSymposium reportSignalingTranslationRoleTarget
2020
Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
Wei J, Alfajaro MM, DeWeirdt PC, Hanna RE, Lu-Culligan WJ, Cai WL, Strine MS, Zhang SM, Graziano VR, Schmitz CO, Chen JS, Mankowski MC, Filler RB, Ravindra NG, Gasque V, de Miguel FJ, Patil A, Chen H, Oguntuyo KY, Abriola L, Surovtseva YV, Orchard RC, Lee B, Lindenbach BD, Politi K, van Dijk D, Kadoch C, Simon MD, Yan Q, Doench JG, Wilen CB. Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection. Cell 2020, 184: 76-91.e13. PMID: 33147444, PMCID: PMC7574718, DOI: 10.1016/j.cell.2020.10.028.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCoronavirusCoronavirus InfectionsCOVID-19Gene Knockout TechniquesGene Regulatory NetworksGenome-Wide Association StudyHEK293 CellsHMGB1 ProteinHost-Pathogen InteractionsHumansSARS-CoV-2Vero CellsVirus InternalizationConceptsSARS-CoV-2 infectionSARS-CoV-2Vesicular stomatitis virusGenome-wide CRISPR screenSWI/SNF chromatinSARS-CoV-2 host factorsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionTherapeutic targetHost factorsCoronavirus disease 2019 (COVID-19) pathogenesisSyndrome coronavirus 2 infectionCRISPR screensHost genesGene productsMiddle East respiratory syndrome CoVCoronavirus 2 infectionGenetic hitsHuman cellsSARS-CoV-2 spikeNovel therapeutic targetPotential therapeutic targetVero E6 cellsSARS-CoV-1Small molecule antagonists
2019
Antisense lncRNA Transcription Mediates DNA Demethylation to Drive Stochastic Protocadherin α Promoter Choice
Canzio D, Nwakeze CL, Horta A, Rajkumar SM, Coffey EL, Duffy EE, Duffié R, Monahan K, O'Keeffe S, Simon MD, Lomvardas S, Maniatis T. Antisense lncRNA Transcription Mediates DNA Demethylation to Drive Stochastic Protocadherin α Promoter Choice. Cell 2019, 177: 639-653.e15. PMID: 30955885, PMCID: PMC6823843, DOI: 10.1016/j.cell.2019.03.008.Peer-Reviewed Original ResearchConceptsDNA demethylationAntisense promoterPromoter choiceHS5-1 enhancerCTCF binding siteNeural circuit assemblyMouse olfactory neuronsPcdhα genesDemethylation functionLncRNA transcriptionSense promoterAntisense transcriptionProtocadherin (Pcdh) αTET3 overexpressionTranscriptional statesAlternate genesPromoter DNAGene choiceDistal enhancerFirst exonPromoterTranscriptionΓ geneGenesOlfactory neurons
2018
Carbodiimide reagents for the chemical probing of RNA structure in cells
Wang PY, Sexton AN, Culligan WJ, Simon MD. Carbodiimide reagents for the chemical probing of RNA structure in cells. RNA 2018, 25: 135-146. PMID: 30389828, PMCID: PMC6298570, DOI: 10.1261/rna.067561.118.Peer-Reviewed Original ResearchConceptsConformation of RNAU nucleotidesIntact cellsChemical probesDimethyl sulfateNucleotides of RNASingle-stranded nucleotidesXist lncRNACellular contextNoncoding RNAsRNA elementsSHAPE reagentsAccessible nucleotidesRNA conformationRNA structureBiological contextChemical probingWatson-Crick faceCellular environmentFunctional roleCarbodiimide reagentRNA nucleotidesRNANucleotidesStructured regionsGaining insight into transcriptome‐wide RNA population dynamics through the chemistry of 4‐thiouridine
Duffy EE, Schofield JA, Simon MD. Gaining insight into transcriptome‐wide RNA population dynamics through the chemistry of 4‐thiouridine. Wiley Interdisciplinary Reviews - RNA 2018, 10: e1513. PMID: 30370679, PMCID: PMC6768404, DOI: 10.1002/wrna.1513.Peer-Reviewed Original ResearchConceptsDifferent RNA populationsRNA populationsNumerous experimental strategiesCellular RNA levelsMetabolic labeling experimentsRNA levelsRNA metabolismRNA turnoverRNA stabilityRNA transcriptionRNA sequencingMetabolic labelingPopulation dynamicsMetabolic labelTargeted incorporationRNA analysisRNA methodWhole cellsC mutationLabeling experimentsExperimental strategiesSequencingAvailable poolGenomeCellsSolid phase chemistry to covalently and reversibly capture thiolated RNA
Duffy EE, Canzio D, Maniatis T, Simon MD. Solid phase chemistry to covalently and reversibly capture thiolated RNA. Nucleic Acids Research 2018, 46: gky556-. PMID: 29986098, PMCID: PMC6101502, DOI: 10.1093/nar/gky556.Peer-Reviewed Original Research
2017
Catching RNAs on chromatin using hybridization capture methods
Machyna M, Simon MD. Catching RNAs on chromatin using hybridization capture methods. Briefings In Functional Genomics 2017, 17: 96-103. PMID: 29126220, PMCID: PMC5888980, DOI: 10.1093/bfgp/elx038.Peer-Reviewed Original ResearchConceptsRNA affinity purificationHybridization capture methodsCross-linked chromatin extractsGenome-wide scaleEnrichment of RNAInteraction of lncRNAsLncRNA localizationChromatin isolationChromatin extractsSite of interactionCapture methodAffinity purificationBiological roleRNA targetsHybridization analysisRNARNA purificationChromatinLncRNAsOligonucleotide hybridizationPurificationDevelopment of methodsProteinCapture experimentsHybridizationInterpreting Reverse Transcriptase Termination and Mutation Events for Greater Insight into the Chemical Probing of RNA
Sexton AN, Wang PY, Rutenberg-Schoenberg M, Simon MD. Interpreting Reverse Transcriptase Termination and Mutation Events for Greater Insight into the Chemical Probing of RNA. Biochemistry 2017, 56: 4713-4721. PMID: 28820243, PMCID: PMC5648349, DOI: 10.1021/acs.biochem.7b00323.Peer-Reviewed Original Research
2015
Probing Xist RNA Structure in Cells Using Targeted Structure-Seq
Fang R, Moss WN, Rutenberg-Schoenberg M, Simon MD. Probing Xist RNA Structure in Cells Using Targeted Structure-Seq. PLOS Genetics 2015, 11: e1005668. PMID: 26646615, PMCID: PMC4672913, DOI: 10.1371/journal.pgen.1005668.Peer-Reviewed Original ResearchConceptsStructure-seqRNA structureRNA conformationNon-coding RNA XISTLong non-coding RNA XISTX-chromosome inactivationSecondary structure mappingRNA of interestXist lncRNAMolecular evolutionC-repeatLncRNA functionsHigher-order structureXist functionRNA functionMammalian cellsMaster regulatorXISTSequencing readsChemical probingParallel sequencingTarget RNARNA XISTRNA basesRNA
2011
The genomic binding sites of a noncoding RNA
Simon MD, Wang CI, Kharchenko PV, West JA, Chapman BA, Alekseyenko AA, Borowsky ML, Kuroda MI, Kingston RE. The genomic binding sites of a noncoding RNA. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 20497-20502. PMID: 22143764, PMCID: PMC3251105, DOI: 10.1073/pnas.1113536108.Peer-Reviewed Original ResearchConceptsDosage compensationCross-linked chromatin extractsMale-specific lethal (MSL) complexLevel of chromatinSpecific genomic sitesImportant regulatory roleHybridization-based techniquesLethal complexLncRNAs bindWide mappingSites of proteinsGenomic sitesChromatin extractsGenomic targetsEndogenous RNAEndogenous lncRNARNA targetsProtein targetsRegulatory roleHybridization analysisRoX2RNAChromatinProteinBinds
2007
The Site-Specific Installation of Methyl-Lysine Analogs into Recombinant Histones
Simon MD, Chu F, Racki LR, de la Cruz CC, Burlingame AL, Panning B, Narlikar GJ, Shokat KM. The Site-Specific Installation of Methyl-Lysine Analogs into Recombinant Histones. Cell 2007, 128: 1003-1012. PMID: 17350582, PMCID: PMC2932701, DOI: 10.1016/j.cell.2006.12.041.Peer-Reviewed Original ResearchConceptsLysine methylationChromatin structureRecombinant histonesContext of chromatinHistone lysine methylationHistone lysine residuesSpecific lysine methylationNucleosome remodelingEffector proteinsPosttranslational modificationsDegree of methylationRecombinant proteinsHistonesLysine residuesMethyl lysineMethylationBiochemical mechanismsSite-specific installationProteinRapid generationNatural counterpartsChromatinPowerful toolAdaptorResidues