Featured Publications
STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts
Zimmer JT, Rosa-Mercado NA, Canzio D, Steitz JA, Simon MD. STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts. Molecular Cell 2021, 81: 4398-4412.e7. PMID: 34520723, PMCID: PMC9020433, DOI: 10.1016/j.molcel.2021.08.019.Peer-Reviewed Original ResearchConceptsPause releaseRNA polymerase II transcriptsRNA polymerase II moleculesCis-acting DNA elementsTATA box-containing promotersPolymerase II transcriptsPromoter-proximal pausingCritical regulatory functionsTranscriptional regulationRNA turnoverTranscriptional controlDNA elementsTranscriptional shutdownPause sitesHyperosmotic stressRegulatory mechanismsRegulatory functionsPrinciples of regulationHormonal stimuliPausingPremature terminationTranscriptsRegulation
2021
Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression
Rosa-Mercado NA, Zimmer JT, Apostolidi M, Rinehart J, Simon MD, Steitz JA. Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression. Molecular Cell 2021, 81: 502-513.e4. PMID: 33400923, PMCID: PMC7867636, DOI: 10.1016/j.molcel.2020.12.002.Peer-Reviewed Original ResearchConceptsWidespread transcriptional repressionTranscriptional repressionPol IIIntegrator complex subunitsRNA polymerase IIGenome-wide lossStress-induced redistributionParental genesTranscriptional outputDoG inductionPolymerase IIChIP sequencingHuman cell linesUpstream geneComplex subunitsPolyadenylation factorsTranscription profilesReadthrough transcriptsCatalytic subunitIntegrator activityCellular stressHyperosmotic stressTranscriptional levelTranscription resultsGenes
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
Solid 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 ResearchMeSH KeywordsAnimalsCell Line, TumorGene ExpressionHEK293 CellsHumansMesylatesMiceMicroRNAsNeuronsRNARNA Polymerase IIStaining and LabelingThiouridine