2024
Cohesin distribution alone predicts chromatin organization in yeast via conserved-current loop extrusion
Yuan T, Yan H, Li K, Surovtsev I, King M, Mochrie S. Cohesin distribution alone predicts chromatin organization in yeast via conserved-current loop extrusion. Genome Biology 2024, 25: 293. PMID: 39543681, PMCID: PMC11566905, DOI: 10.1186/s13059-024-03432-2.Peer-Reviewed Original ResearchConceptsTopologically associating domainsLoop extrusionTopologically associating domains boundariesNon-vertebrate eukaryotesChIP-seq dataChromatin spatial organizationTree of lifeHi-C mapsBinds CTCFCohesin distributionTAD boundariesCTCF sitesChromatin organizationDNA sequencesCTCFCohesinYeastChromatinSpatial organizationEukaryotesGenomeResultsToVertebratesExtrusion factorsOrganizationA-tisket, a-tasket, what a beautiful nuclear basket
Lusk C, King M. A-tisket, a-tasket, what a beautiful nuclear basket. Cell 2024, 187: 5225-5227. PMID: 39303690, DOI: 10.1016/j.cell.2024.08.030.Peer-Reviewed Original ResearchIdentifying topologically associating domains using differential kernels
Maisuradze L, King M, Surovtsev I, Mochrie S, Shattuck M, O’Hern C. Identifying topologically associating domains using differential kernels. PLOS Computational Biology 2024, 20: e1012221. PMID: 39008525, PMCID: PMC11249266, DOI: 10.1371/journal.pcbi.1012221.Peer-Reviewed Original ResearchConceptsTopologically associating domainsHi-C mapsFalse discovery rateChromatin conformation capture techniquesEnhancer-promoter interactionsLow false discovery rateSelf-interacting regionsStructure of chromatinRegulate gene expressionAverage contact probabilitiesHi-CLocus IDNA transcriptionGene expressionChromatinDiscovery rateContact probabilityBiological phenomenaState-of-the-artKernel-based techniqueComputer visionReplicationCorrelated changesDisease statesCapture techniquesThe condensation of HP1α/Swi6 imparts nuclear stiffness
Williams J, Surovtsev I, Schreiner S, Chen Z, Raiymbek G, Nguyen H, Hu Y, Biteen J, Mochrie S, Ragunathan K, King M. The condensation of HP1α/Swi6 imparts nuclear stiffness. Cell Reports 2024, 43: 114373. PMID: 38900638, PMCID: PMC11348953, DOI: 10.1016/j.celrep.2024.114373.Peer-Reviewed Original ResearchSingle-molecule imagingBiomolecular condensatesSeparation-of-function alleleHeterochromatin protein HP1aChromatin-bound moleculesHigh-resolution live-cell imagingLive-cell imagingCondensationHeterochromatin domainsMethylated nucleosomesSwi6Nuclear stiffnessForce spectroscopyChromatin meshworkCellular organizationCell mechanicsDynamic poolEffect of loops on the mean-square displacement of Rouse-model chromatin
Yuan T, Yan H, Bailey M, Williams J, Surovtsev I, King M, Mochrie S. Effect of loops on the mean-square displacement of Rouse-model chromatin. Physical Review E 2024, 109: 044502. PMID: 38755928, DOI: 10.1103/physreve.109.044502.Peer-Reviewed Original ResearchConceptsStretching exponentConsistent with recent experimentsTopologically associating domainsMean square displacementRecent experimentsLoop extrusionExponent valuesTAD formationTree of lifeDynamics of chromatinExponentEffects of loopChromatin lociChromatin dynamicsRouse modelChromatin organizationChromatin mobilityGene locusContact mapsDynamicsChromatinLoopPolymer dynamicsLociPolymer simulations
2023
It is time to reconsider the culture of volunteerism in undergraduate research
King M. It is time to reconsider the culture of volunteerism in undergraduate research. Journal Of Cell Science 2023, 136 PMID: 38158844, DOI: 10.1242/jcs.261865.Peer-Reviewed Original ResearchDynamic regulation of LINC complex composition and function across tissues and contexts
King M. Dynamic regulation of LINC complex composition and function across tissues and contexts. FEBS Letters 2023, 597: 2823-2832. PMID: 37846646, DOI: 10.1002/1873-3468.14757.Peer-Reviewed Original ResearchConceptsLINC complex componentsLINC complexLinker of nucleoskeletonProtein turnover mechanismsCytoplasmic intermediate filament networkIntermediate filament networkCytoskeleton (LINC) complexComplex componentsNuclear laminaCellular contextCytoplasmic cytoskeletonCell biologistsDynamic regulationNuclear envelopeRegulated expressionTurnover mechanismsFilament networkSplice variantsCell typesProtein configurationUnique functionCytoskeletonConcept of mechanotransductionComplexesNucleoskeletonAn ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity
Ader N, Chen L, Surovtsev I, Chadwick W, Rodriguez E, King M, Lusk C. An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity. Nature Cell Biology 2023, 25: 1465-1477. PMID: 37783794, PMCID: PMC11365527, DOI: 10.1038/s41556-023-01235-4.Peer-Reviewed Original ResearchConceptsSpindle pole body proteinNuclear envelope barrierESCRT-III proteinsNuclear pore complexSpindle pole bodyNucleocytoplasmic compartmentalizationESCRT functionPore complexPole bodyDistinct complementNuclear compartmentNuclear integrityTransport proteinsMolecular mechanismsRemodelling mechanismProteinBody proteinAcetyl-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 signalsHistonesBRD2Elasticity of spheres with buckled surfaces
Tian Y, McCarthy M, King M, Mochrie S. Elasticity of spheres with buckled surfaces. Physical Review E 2023, 107: 065003. PMID: 37464712, DOI: 10.1103/physreve.107.065003.Peer-Reviewed Original ResearchSpherical voidsElastic energyCore-shell systemElastic spheresLinear elastic problemsSurface deformationBulk elastic energyPoisson's ratioShear modulusElastic problemShape phase diagramSpherical harmonic degreeExterior shellSphere shapePhase diagramHarmonicsElasticityVoidsHarmonic degreeClosed-form expressionsSpherical coreLoops and the activity of loop extrusion factors constrain chromatin dynamics
Bailey M, Surovtsev I, Williams J, Yan H, Yuan T, Li K, Duseau K, Mochrie S, King M. Loops and the activity of loop extrusion factors constrain chromatin dynamics. Molecular Biology Of The Cell 2023, 34: ar78. PMID: 37126401, PMCID: PMC10398873, DOI: 10.1091/mbc.e23-04-0119.Peer-Reviewed Original ResearchConceptsChromatin dynamicsChromatin mobilityChromatin conformation capture experimentsINO80 chromatin remodelerSystematic genetic perturbationsDynamics of chromatinSWI/SNFChromatin fluctuationsCondensin complexRSC complexChromatin remodelersFission yeastChromosome structureChromatin polymerExtrusion factorsChromatin motionGenetic perturbationsThree-dimensional structureDNA structureChromatinCohesinPolymer simulationsIntroduction of loopsKey roleActive process
2019
RNA–DNA Hybrids Support Recombination-Based Telomere Maintenance in Fission Yeast
Hu Y, Bennett HW, Liu N, Moravec M, Williams JF, Azzalin CM, King MC. RNA–DNA Hybrids Support Recombination-Based Telomere Maintenance in Fission Yeast. Genetics 2019, 213: 431-447. PMID: 31405990, PMCID: PMC6781888, DOI: 10.1534/genetics.119.302606.Peer-Reviewed Original ResearchConceptsTelomeric repeat-containing RNAHomology-directed repairFission yeastR-loopsLinear chromosomesTelomere maintenanceRecombination-based telomere maintenanceTelomerase-independent telomere maintenanceShelterin component Rap1State of telomeresTelomeric R-loopsRepeat-containing RNARNA-DNA hybridsDeletion of Rap1Telomerase-independent mechanismChromosome endsShelterin componentsGrowth crisisTelomerase functionTelomeric DNARecombination factorsSubset of cancersTelomeresAlternative lengtheningShort telomeresAblation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosis
Stewart RM, Rodriguez EC, King MC. Ablation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosis. Molecular Biology Of The Cell 2019, 30: 1664-1675. PMID: 31091167, PMCID: PMC6727752, DOI: 10.1091/mbc.e18-07-0438.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiomegalyCell AdhesionCell Nucleus ShapeDNA-Binding ProteinsFibrosisGene DeletionIntegrinsMAP Kinase Signaling SystemMembrane ProteinsMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesMyocardiumNuclear EnvelopeProto-Oncogene Proteins c-aktSarcomeresTelomere-Binding ProteinsTransforming Growth Factor betaConceptsLINC complexType laminsInner nuclear membrane protein MAN1Nuclear envelopeA-type laminsSarcomeric contractile apparatusNuclear laminaDisease etiologyProfibrotic signalingCytoskeletal linkageAKT/MAPK signalingCardiomyocyte cytoskeletonPlasma membraneMAPK signalingNegative regulatorAntagonistic rolesTGFβ signalingLaminsCellular adhesionSignalingCardiac hypertrophySUN2Human cardiomyopathyHypertrophy markersContractile apparatus
2018
Integration of Biochemical and Mechanical Signals at the Nuclear Periphery: Impacts on Skin Development and Disease
Stewart R, King M, Horsley V. Integration of Biochemical and Mechanical Signals at the Nuclear Periphery: Impacts on Skin Development and Disease. Stem Cell Biology And Regenerative Medicine 2018, 263-292. DOI: 10.1007/978-3-319-16769-5_11.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNuclear laminaIntegral inner nuclear membrane proteinsInner nuclear membrane proteinSkin developmentMechanical signalsNuclear membrane proteinsInner nuclear membraneIntegration of biochemicalGenome integrityNuclear peripheryTranscriptional outputNuclear laminsAssociated chromatinMembrane proteinsNuclear interiorTissue-level mechanicsGene expressionNuclear membraneSkin homeostasisKeratinocyte differentiationMechanical inputChromatinLaminsLaminaProteinRev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks
Leland BA, Chen AC, Zhao AY, Wharton RC, King MC. Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks. ELife 2018, 7: e33402. PMID: 29697047, PMCID: PMC5945276, DOI: 10.7554/elife.33402.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksDouble-strand breaksLong-range resectionPARPi resistanceBRCA1-deficient cellsHomology-directed repairExonuclease Exo1RecQ helicaseNucleolytic processingMicroscopy assaysREV7Cancer cellsMachineryPreclinical modelsResectionPolymerase inhibitorsPathwayCellsRecQOrthologuesHelicaseExo1AssaysDNA2BreaksThe Molecular Composition and Function of the Nuclear Periphery and Its Impact on the Genome
Lusk C, King M. The Molecular Composition and Function of the Nuclear Periphery and Its Impact on the Genome. 2018, 35-62. DOI: 10.1007/978-3-319-71614-5_2.Peer-Reviewed Original ResearchNuclear peripheryNuclear subcompartmentsIntegral inner nuclear membrane proteinsInner nuclear membrane proteinSpecific genic regionsRepressive histone marksNuclear membrane proteinsGene-poor chromatinModern genomic analysesGenome stabilityHistone marksNuclear architectureGenic regionsTranscriptional outputNuclear laminsGene positionMembrane proteinsGenomic analysisDevelopmental inputsMolecular insightsMolecular componentsGenomeModel systemMolecular compositionCurrent understanding
2016
TeloPCR‐seq: a high‐throughput sequencing approach for telomeres
Bennett HW, Liu N, Hu Y, King MC. TeloPCR‐seq: a high‐throughput sequencing approach for telomeres. FEBS Letters 2016, 590: 4159-4170. PMID: 27714790, PMCID: PMC5561429, DOI: 10.1002/1873-3468.12444.Peer-Reviewed Original ResearchImproved Determination of Subnuclear Position Enabled by Three-Dimensional Membrane Reconstruction
Zhao Y, Schreiner SM, Koo PK, Colombi P, King MC, Mochrie SG. Improved Determination of Subnuclear Position Enabled by Three-Dimensional Membrane Reconstruction. Biophysical Journal 2016, 111: 19-24. PMID: 27410730, PMCID: PMC4945324, DOI: 10.1016/j.bpj.2016.05.036.Peer-Reviewed Original ResearchConceptsChromatin biologyLac operator arraysMembrane marker proteinsNuclear positionBroad practical utilityNuclear volumeNuclear peripheryOrganelle shapeChromatin markersTranscriptional regulationSubnuclear positionLacI-GFPDNA repairIndividual lociNuclear compartmentPopulation of cellsNuclear envelopeLocus positionParticular locusMarker proteinsImage analysis pipelineLociCell populationsAnalysis pipelineBiological accuracy
2015
The tethering of chromatin to the nuclear envelope supports nuclear mechanics
Schreiner SM, Koo PK, Zhao Y, Mochrie SG, King MC. The tethering of chromatin to the nuclear envelope supports nuclear mechanics. Nature Communications 2015, 6: 7159. PMID: 26074052, PMCID: PMC4490570, DOI: 10.1038/ncomms8159.Peer-Reviewed Original ResearchConceptsNuclear mechanicsRole of chromatinOptical tweezersWild-type nucleiNetwork of lipidsCytoskeletal forcesNuclear laminaCytoskeletal dynamicsMechanical defensesMembrane tethersDeformable nucleiNuclear envelopeChromatinNuclear shapeIsolated nucleiIndividual mechanical contributionsMembrane resultsNucleusTweezersMechanicsLaminsProteinTetheringLaminaDefenseNuclear–cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions
Stewart RM, Zubek AE, Rosowski KA, Schreiner SM, Horsley V, King MC. Nuclear–cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions. Journal Of Cell Biology 2015, 209: 403-418. PMID: 25963820, PMCID: PMC4427780, DOI: 10.1083/jcb.201502024.Peer-Reviewed Original ResearchConceptsIntercellular adhesionNuclear positionEpidermal tissue integrityLinker of nucleoskeletonCross talkPrimary mouse keratinocytesCytoskeleton (LINC) complexCytoplasmic cytoskeletonAdhesion functionMicrotubule networkDefective adhesionCytoskeletonSUN2Mouse keratinocytesTissue integrityFollicle structureEpidermal keratinocytesAdhesionNucleoskeletonCellsKeratinocytesAdhesion formationNucleusIntegrityComplexes