2025
Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination
Wu L, Yadavalli A, Senigl F, Matos-Rodrigues G, Xu D, Pintado-Urbanc A, Simon M, Wu W, Nussenzweig A, Schatz D. Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination. Molecular Cell 2025 PMID: 40049160, DOI: 10.1016/j.molcel.2025.02.007.Peer-Reviewed Original ResearchRNA polymerase IITranscription-coupled nucleotide excision repairActivation-induced deaminaseClass switch recombinationSomatic hypermutationRNA polymerase II elongation complexDownstream of transcription start sitesRNA polymerase II transcriptionTranscription start siteSwitch recombinationMammalian B cellsImmunoglobulin (Ig) genesDNA cytidine deaminaseNucleotide excision repairPolymerase IISerine 5Transcribed genesTranscription elongationElongation complexStart siteGenetic screeningELOF1Excision repairTranscriptionProximity partners
2024
Piwi regulates the usage of alternative transcription start sites in the Drosophila ovary
Chen J, Liu N, Qi H, Neuenkirchen N, Huang Y, Lin H. Piwi regulates the usage of alternative transcription start sites in the Drosophila ovary. Nucleic Acids Research 2024, 53: gkae1160. PMID: 39657757, PMCID: PMC11724274, DOI: 10.1093/nar/gkae1160.Peer-Reviewed Original ResearchTranscription start siteTranscription start site usageFacilitates chromatin transcriptionDrosophila ovaryOvarian somatic cellsStart siteCap analysis of gene expression sequencingAlternative transcription start sitesSomatic cellsPol II initiationRNA polymerase IIAlternative transcription initiationRNA-binding proteinsCultured ovarian somatic cellsGene expression sequencingMRNA elongationPolymerase IIPol IITranscription initiationChromatin transcriptionTranscriptional regulationExpressed sequencesMutant ovariesPIWICap analysisHEXIM1 Regulates Early Erythropoiesis and Participates in Multiple Complexes in Erythroid Cells
Rahman N, Abid D, Lv X, Murphy K, Getman M, McGrath K, Gallagher P, Narla M, Blanc L, Palis J, Mello S, Steiner L. HEXIM1 Regulates Early Erythropoiesis and Participates in Multiple Complexes in Erythroid Cells. Blood 2024, 144: 536. DOI: 10.1182/blood-2024-209259.Peer-Reviewed Original ResearchRNA polymerase IIErythroid gene expressionGene expressionTerminal erythroid maturationEarly erythropoiesisErythroid cellsErythroid maturationRegulation of gene expressionProgenitor cellsImpaired erythroid differentiationRNAPII pausingGenomic contextPolymerase IIRepress transcriptionSteady-state erythropoiesisErythroid progenitor cellsCD34+ HSPCsRegulatory domainBinding partnersErythropoiesis in vivoBlood cell countColony-forming cellsLow red blood cell countSubnuclear bodiesErythroid progenitor differentiationEmerging and re-emerging themes in co-transcriptional pre-mRNA splicing
Carrocci T, Neugebauer K. Emerging and re-emerging themes in co-transcriptional pre-mRNA splicing. Molecular Cell 2024, 84: 3656-3666. PMID: 39366353, PMCID: PMC11463726, DOI: 10.1016/j.molcel.2024.08.036.Peer-Reviewed Original ResearchConceptsPre-mRNA splicingCo-transcriptional pre-mRNA splicingCo-transcriptional RNA foldingCo-transcriptional processesRNA polymerase IIPre-messenger RNAFunctional messenger RNAsCapping enzymePolymerase IIDelayed splicingPolyadenylation machinerySplicing eventsPre-mRNAGene regulationMacromolecular machinesRNA foldingRNA synthesisMRNA isoformsProtein productionGene expressionSplicingRNARegulatory importanceCross-regulationMessenger RNADormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency
Goehring L, Keegan S, Lahiri S, Xia W, Kong M, Jimenez-Sainz J, Gupta D, Drapkin R, Jensen R, Smith D, Rothenberg E, Fenyö D, Huang T. Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency. Nature Communications 2024, 15: 4716. PMID: 38830843, PMCID: PMC11148086, DOI: 10.1038/s41467-024-48286-1.Peer-Reviewed Original ResearchConceptsTranscription termination sitesTranscription-replication conflictsDormant originsReplication stressElongating RNA polymerase IITermination sitesResponse to replication stressRNA polymerase IIR-loop formationTumor suppressor proteinPolymerase IIR-loopsLong genesRNase H2Transcription initiationOK-seqGenomic sitesSuppressor proteinCellular genomeBRCA2 deficiencyOrigin firingSuper-resolution microscopyGenomic instabilityDormant origin firingTranscriptionDNA lesion bypass and the stochastic dynamics of transcription-coupled repair
Nicholson M, Anderson C, Odom D, Aitken S, Taylor M. DNA lesion bypass and the stochastic dynamics of transcription-coupled repair. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2403871121. PMID: 38717857, PMCID: PMC11098089, DOI: 10.1073/pnas.2403871121.Peer-Reviewed Original ResearchConceptsTranscription-coupled repairRNA polymerase IIDistribution of mutationsStalling of RNA polymerase IITranscription-coupled repair (TCRDNA damageGene expressionBarriers to gene expressionSites of DNA damageGenome-wide distributionBarrier to transcriptionDamaged DNA strandMammalian model systemsDNA lesion bypassGene bodiesPolymerase IIRNA polymeraseGenetic integrityGene productsDNA base damageLesion bypassAlkylation damageDNA strandsBypass lesionsMutationsMECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons
Liu Y, Flamier A, Bell G, Diao A, Whitfield T, Wang H, Wu Y, Schulte F, Friesen M, Guo R, Mitalipova M, Liu X, Vos S, Young R, Jaenisch R. MECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons. Neuron 2024, 112: 1943-1958.e10. PMID: 38697112, DOI: 10.1016/j.neuron.2024.04.007.Peer-Reviewed Original ResearchPromoter-proximal regionRNA polymerase IIPolymerase IIHuman neuronsMethylated DNA binding protein MeCP2RNA Pol IIWild-typeLoss of gene activityAutism risk genesPol IIPositive cofactorCpG islandsTranscriptional regulationModulate transcriptionProtein MeCP2Patient mutationsNeurodevelopmental disorder Rett syndromeGene activationRisk genesProteomic analysisNeuronal genesRett syndromeGene expressionGenesRNACdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila
Liao J, Chung H, Shih C, Wong K, Dutta D, Nil Z, Burns C, Kanca O, Park Y, Zuo Z, Marcogliese P, Sew K, Bellen H, Verheyen E. Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila. Nature Communications 2024, 15: 3326. PMID: 38637532, PMCID: PMC11026413, DOI: 10.1038/s41467-024-47623-8.Peer-Reviewed Original ResearchConceptsMitochondrial fissionRNA polymerase IINon-nuclear functionsDrp1-mediated fissionPhosphorylation of Drp1Elevated levels of ROSMitochondrial kinaseBang sensitivityLevels of PINK1Polymerase IIFly lifespanPhosphorylated Drp1PINK1 deficiencyDrp1 phosphorylationTranscriptional controlElongated mitochondriaLevels of ROSOverexpression of CDK8CDK8Drp1Mitochondrial dysmorphologyBehavioral defectsPINK1DrosophilaCytoplasmTranscription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape
Boddu P, Gupta A, Roy R, De La Peña Avalos B, Olazabal-Herrero A, Neuenkirchen N, Zimmer J, Chandhok N, King D, Nannya Y, Ogawa S, Lin H, Simon M, Dray E, Kupfer G, Verma A, Neugebauer K, Pillai M. Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape. Molecular Cell 2024, 84: 1475-1495.e18. PMID: 38521065, PMCID: PMC11061666, DOI: 10.1016/j.molcel.2024.02.032.Peer-Reviewed Original ResearchRate of RNA polymerase IIChromatin landscapeElongation defectsElongation rate of RNA polymerase IIImpaired protein-protein interactionsSplicing of pre-messenger RNATranscription elongation defectsRNA polymerase IIProtein-protein interactionsPre-messenger RNACancer-associated mutationsIsogenic cell linesSin3/HDAC complexGene bodiesPolymerase IIChromatin accessibilityH3K4me3 markChromatin changesMutant SF3B1ChromatinMutant mouse modelsEpigenetic disordersEpigenetic factorsHuman diseasesMutant state
2023
Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin
Pownall M, Miao L, Vejnar C, M'Saad O, Sherrard A, Frederick M, Benitez M, Boswell C, Zaret K, Bewersdorf J, Giraldez A. Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin. Science 2023, 381: 92-100. PMID: 37410825, PMCID: PMC10372697, DOI: 10.1126/science.ade5308.Peer-Reviewed Original ResearchConceptsZygotic genome activationTranscriptional elongationExpansion microscopyRNA polymerase IIChromatin regulatory factorsEnhancer-promoter contactsGenome activationChromatin organizationNuclear organizationPolymerase IIPol IIFactor NanogTranscription factorsGene expressionRegulatory factorsChromatinNanoscale organizationNanogTranscriptionElongationNucleosomesUniversal processPromoterEmbryosEnhancerDOT1L promotes spermatid differentiation by regulating expression of genes required for histone-to-protamine replacement
Malla A, Rainsford S, Smith Z, Lesch B. DOT1L promotes spermatid differentiation by regulating expression of genes required for histone-to-protamine replacement. Development 2023, 150 PMID: 37082969, PMCID: PMC10259660, DOI: 10.1242/dev.201497.Peer-Reviewed Original ResearchConceptsHistone replacementMale sterilityProtamine exchangeSpermatid differentiationHistone H3 lysine 79Chromatin remodeling factorsRNA polymerase IIH3 lysine 79Expression of genesMature sperm headSperm headPostmeiotic germ cellsHistone methyltransferase DOT1LPolymerase IILysine 79Embryonic lethalityRemodeling factorsProtamine transitionProtamine replacementTranscriptional dysregulationMethyltransferase DOT1LIndispensable regulatorDOT1LHistonesGerm cells
2022
Better late than never: A unique strategy for late gene transcription in the beta- and gammaherpesviruses
Dremel S, Didychuk A. Better late than never: A unique strategy for late gene transcription in the beta- and gammaherpesviruses. Seminars In Cell And Developmental Biology 2022, 146: 57-69. PMID: 36535877, PMCID: PMC10101908, DOI: 10.1016/j.semcdb.2022.12.001.Peer-Reviewed Original ResearchConceptsViral transcriptional activityViral preinitiation complexPol IITranscription of late genesGene transcriptionCellular RNA polymerase IITATA-binding proteinRNA polymerase IIModified TATA boxCis-acting elementsSubfamily of herpesvirusesPolymerase IITATA boxPreinitiation complexConsensus sequenceLate genesTranscriptional activityGene promoterLytic replicationGenesTemporal cascadeTranscriptionViral mimicPolPromotermiRNA‐encapsulated abiotic materials and biovectors for cutaneous and oral wound healing: Biogenesis, mechanisms, and delivery nanocarriers
Dey A, Yousefiasl S, Kumar A, Moghaddam F, Rahimmanesh I, Samandari M, Jamwal S, Maleki A, Mohammadi A, Rabiee N, Paiva‐Santos A, Tamayol A, Sharifi E, Makvandi P. miRNA‐encapsulated abiotic materials and biovectors for cutaneous and oral wound healing: Biogenesis, mechanisms, and delivery nanocarriers. Bioengineering & Translational Medicine 2022, 8: e10343. PMID: 36684081, PMCID: PMC9842058, DOI: 10.1002/btm2.10343.Peer-Reviewed Original ResearchBromodomains regulate dynamic targeting of the PBAF chromatin-remodeling complex to chromatin hubs
Kenworthy C, Haque N, Liou S, Chandris P, Wong V, Dziuba P, Lavis L, Liu W, Singer R, Coleman R. Bromodomains regulate dynamic targeting of the PBAF chromatin-remodeling complex to chromatin hubs. Biophysical Journal 2022, 121: 1738-1752. PMID: 35364106, PMCID: PMC9117891, DOI: 10.1016/j.bpj.2022.03.027.Peer-Reviewed Original ResearchConceptsChromatin remodelersChromatin statePBAF chromatin-remodeling complexSingle-molecule fluorescence microscopy studiesDifferent chromatin statesChromatin-remodeling complexRNA polymerase IIChromatin hubTranscriptional burstingPolymerase IIAcetylated nucleosomesFluorescence microscopy studiesPBAFBromodomainsNucleosomesChromatin stabilityLive cellsStable engagementRemodelersDynamic targetingDirect roleChromatinImaging revealsTargetingGenomeLive-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer
Yi E, Gujar A, Guthrie M, Kim H, Zhao D, Johnson K, Amin S, Costa M, Yu Q, Das S, Jillette N, Clow P, Cheng A, Verhaak R. Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer. Cancer Discovery 2022, 12: 468-483. PMID: 34819316, PMCID: PMC8831456, DOI: 10.1158/2159-8290.cd-21-1376.Peer-Reviewed Original ResearchConceptsExtrachromosomal DNA elementsDNA elementsUneven segregationRNA polymerase IILive-cell imagingPolymerase IIOffspring cellsGene transcriptionCell line modelsEcDNAsRandom segregationGenetic materialLiving cellsCopy numberLive cellsIndividual cellsTumor evolutionMitosisInheritance patternBreakpoint sequencesIssue featureTranscriptionFluorescent markersPatient tissuesCellsIg Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences.
Tarsalainen A, Maman Y, Meng FL, Kyläniemi MK, Soikkeli A, Budzyńska P, McDonald JJ, Šenigl F, Alt FW, Schatz DG, Alinikula J. Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences. The Journal Of Immunology 2022, 208: 143-154. PMID: 34862258, PMCID: PMC8702490, DOI: 10.4049/jimmunol.2100923.Peer-Reviewed Original ResearchConceptsPol IIMutating geneSomatic hypermutationTarget genesChicken DT40 B cellsRNA polymerase II stallingIg genesHistone variant H3.3Locus-specific targetingPol II occupancyAID-mediated mutationsDT40 B cellsRNA polymerase IILevels of H3K27acFull-length transcriptsVariant H3.3Antisense transcriptionTranscriptional outputPolymerase IIGenetic diversityMechanistic basisBurkitt's lymphoma cellsGeneration of AbsGenesDIVAC
2021
Regulation of RNA polymerase II activity is essential for terminal erythroid maturation
Murphy ZC, Murphy K, Myers J, Getman M, Couch T, Schulz VP, Lezon-Geyda K, Palumbo C, Yan H, Mohandas N, Gallagher PG, Steiner LA. Regulation of RNA polymerase II activity is essential for terminal erythroid maturation. Blood 2021, 138: 1740-1756. PMID: 34075391, PMCID: PMC8569412, DOI: 10.1182/blood.2020009903.Peer-Reviewed Original ResearchConceptsRNA polymerase IIRNA polymerase II activityTerminal erythroid maturationPolymerase II activityPolymerase IIErythroid maturationHuman erythroblastsGene expressionTerminal maturationII activityStage-specific regulationHistone posttranslational modificationsTransposase-accessible chromatinErythroid-specific genesAccumulation of heterochromatinHigh-throughput sequencingLevel of transcriptionLate-stage erythroblastsEssential biologic processesAccessible chromatinHistone marksTranscription elongationChromatin structureTranscriptional repressionChromatin immunoprecipitationHyperosmotic 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
2020
The gammaherpesviral TATA-box-binding protein directly interacts with the CTD of host RNA Pol II to direct late gene transcription
Castañeda A, Didychuk A, Louder R, McCollum C, Davis Z, Nogales E, Glaunsinger B. The gammaherpesviral TATA-box-binding protein directly interacts with the CTD of host RNA Pol II to direct late gene transcription. PLOS Pathogens 2020, 16: e1008843. PMID: 32886723, PMCID: PMC7498053, DOI: 10.1371/journal.ppat.1008843.Peer-Reviewed Original ResearchConceptsTATA box-binding proteinRNA polymerase IIN-terminal domainPol IIPolymerase IICellular TATA box binding proteinHost RNA polymerase IIRecruitment of RNA polymerase IIGene transcriptionLate gene transcriptionPol II recruitmentProtein interaction studiesProtein-protein contactsC-terminal domainEukaryotic transcriptionPolymerase recruitmentHuman cytomegalovirusPreinitiation complexHost transcriptionRNA PolLate genesMicroscopy-based imagingKaposi's sarcoma-associated virusTranscriptional activityPromoter recognitionDiNeR: a Differential graphical model for analysis of co-regulation Network Rewiring
Zhang J, Liu J, Lee D, Lou S, Chen Z, Gürsoy G, Gerstein M. DiNeR: a Differential graphical model for analysis of co-regulation Network Rewiring. BMC Bioinformatics 2020, 21: 281. PMID: 32615918, PMCID: PMC7333332, DOI: 10.1186/s12859-020-03605-3.Peer-Reviewed Original ResearchConceptsCo-regulation networkCo-regulatory networkNetwork rewiringDisease regulatorsGenome-wide binding profilesGM12878 cell lineRNA polymerase IITumor suppressor BRCA1Transcription factor bindsChIP-seq dataDifferential graphical modelsBinding profileComplete binding profilesKey TFsPolymerase IIHub regulatorsPhenotypic variationFactor bindsGene expressionExpression changesCancerous stateRisk genesRegulatorCell linesCoordinated manner
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