2025
p53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells
Miller K, Li B, Pierce-Hoffman H, Patel S, Lei X, Rajesh A, Teneche M, Havas A, Gandhi A, Macip C, Lyu J, Victorelli S, Woo S, Lagnado A, LaPorta M, Liu T, Dasgupta N, Li S, Davis A, Korotkov A, Hultenius E, Gao Z, Altman Y, Porritt R, Garcia G, Mogler C, Seluanov A, Gorbunova V, Kaech S, Tian X, Dou Z, Chen C, Passos J, Adams P. p53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells. Nature Communications 2025, 16: 2229. PMID: 40044657, PMCID: PMC11882782, DOI: 10.1038/s41467-025-57229-3.Peer-Reviewed Original ResearchConceptsCytoplasmic chromatin fragmentsDNA repairGenome integrityChromatin fragmentsNuclear DNA damage signalsGenomic instabilitySenescent cellsActivation of p53Controlling DNA repairATM-dependent mannerDNA damage signalingSignatures of agingAge-associated accumulationActivate p53P53 activationHallmarks of agingDamage signalingAge-associated diseasesSignaling circuitsP53Molecular circuitsEnhanced DNA repairGenomePharmacological inhibitionAge-associated inflammationThe human and non-human primate developmental GTEx projects
Bell T, Blanchard T, Hernandez R, Linn R, Taylor D, VonDran M, Ahooyi T, Beitra D, Bernieh A, Delaney M, Faith M, Fattahi E, Footer D, Gilbert M, Guambaña S, Gulino S, Hanson J, Hattrell E, Heinemann C, Kreeb J, Leino D, Mcdevitt L, Palmieri A, Pfeiffer M, Pryhuber G, Rossi C, Rasool I, Roberts R, Salehi A, Savannah E, Stachowicz K, Stokes D, Suplee L, Van Hoose P, Wilkins B, Williams-Taylor S, Zhang S, Ardlie K, Getz G, Lappalainen T, Montgomery S, Aguet F, Anderson L, Bernstein B, Choudhary A, Domenech L, Gaskell E, Johnson M, Liu Q, Marderstein A, Nedzel J, Okonda J, Padhi E, Rosano M, Russell A, Walker B, Sestan N, Gerstein M, Milosavljevic A, Borsari B, Cho H, Clarke D, Deveau A, Galeev T, Gobeske K, Hameed I, Huttner A, Jensen M, Jiang Y, Li J, Liu J, Liu Y, Ma J, Mane S, Meng R, Nadkarni A, Ni P, Park S, Petrosyan V, Pochareddy S, Salamon I, Xia Y, Yates C, Zhang M, Zhao H, Conrad D, Feng G, Brady F, Boucher M, Carbone L, Castro J, del Rosario R, Held M, Hennebold J, Lacey A, Lewis A, Lima A, Mahyari E, Moore S, Okhovat M, Roberts V, de Castro S, Wessel B, Zaniewski H, Zhang Q, Arguello A, Baroch J, Dayal J, Felsenfeld A, Ilekis J, Jose S, Lockhart N, Miller D, Minear M, Parisi M, Price A, Ramos E, Zou S. The human and non-human primate developmental GTEx projects. Nature 2025, 637: 557-564. PMID: 39815096, DOI: 10.1038/s41586-024-08244-9.Peer-Reviewed Original ResearchConceptsChromatin accessibility dataFunctional genomic studiesWhole-genome sequencingEffects of genetic variationSpatial gene expression profilesNon-human primatesGenotype-Tissue ExpressionGene expression profilesGenomic studiesGene regulationGenetic dataGenetic variationGenomic researchDonor diversityCommunity engagementHuman evolutionEarly developmental defectsGene expressionCell statesDevelopmental programmeHuman diseasesExpression profilesAdult tissuesDevelopmental defectsSingle-cellGuidelines to Analyze ChIP-Seq Data: Journey Through QC and Analysis Considerations
De Kumar B, Krishnan J. Guidelines to Analyze ChIP-Seq Data: Journey Through QC and Analysis Considerations. Methods In Molecular Biology 2025, 2889: 193-206. PMID: 39745614, DOI: 10.1007/978-1-0716-4322-8_14.Peer-Reviewed Original ResearchConceptsChIP-seqChIP-seq analysisQC metricsProperties of transcription factorsNext-generation sequencing approachChIP-seq experimentsStudy DNA-protein interactionsGene regulatory propertiesDNA-protein interactionsENCODE consortiumChromatin stateSequencing approachTranscription factorsChromatinGenesNext-generationImmunoprecipitationSequence
2024
An integrative TAD catalog in lymphoblastoid cell lines discloses the functional impact of deletions and insertions in human genomes.
Li C, Bonder M, Syed S, Jensen M, Gerstein M, Zody M, Chaisson M, Talkowski M, Marschall T, Korbel J, Eichler E, Lee C, Shi X. An integrative TAD catalog in lymphoblastoid cell lines discloses the functional impact of deletions and insertions in human genomes. Genome Research 2024, 34: 2304-2318. PMID: 39638559, PMCID: PMC11694747, DOI: 10.1101/gr.279419.124.Peer-Reviewed Original ResearchMeSH KeywordsCell LineChromatinGene Expression RegulationGenome, HumanHumansMutagenesis, InsertionalConceptsTopologically associating domainsTopologically associating domains boundariesImpact of structural variantsLymphoblastoid cell linesStructural variantsHuman genomeGene regulationAdjacent TADsHuman lymphoblastoid cell linesCell linesSub-TADGenomic structureInsulate genesChromatin architectureImpact of deletionChromatin structureGenomeAberrant regulationAnalysis pipelineMammalian speciesGenesCCREsFunctional impactChromatinRegulationSingle-nucleus multi-omics analyses reveal cellular and molecular innovations in the anterior cingulate cortex during primate evolution
Yuan J, Dong K, Wu H, Zeng X, Liu X, Liu Y, Dai J, Yin J, Chen Y, Guo Y, Luo W, Liu N, Sun Y, Zhang S, Su B. Single-nucleus multi-omics analyses reveal cellular and molecular innovations in the anterior cingulate cortex during primate evolution. Cell Genomics 2024, 4: 100703. PMID: 39631404, PMCID: PMC11701334, DOI: 10.1016/j.xgen.2024.100703.Peer-Reviewed Original ResearchConceptsChromatin accessibilitySingle-nucleusGene expressionTranscription factor bindingPatterns of gene expressionSingle-nucleus resolutionCell lineage originACC gene expressionPrimate evolutionMulti-omics analysisAnterior cingulate cortexFactor bindingEvolutionary roleFunctional innovationSequence changesMolecular innovationsVon Economo neuronsMolecular regulationMarker genesPublished mouse dataCell typesChromatinMolecular identityHuman originCingulate cortexCohesin 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 factorsOrganizationKLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes
Wang A, Fairhurst A, Liu K, Wakeland B, Barnes S, Malladi V, Viswanathan K, Arana C, Dozmorov I, Singhar A, Du Y, Imam M, Moses A, Chen C, Sunkavalli A, Casco J, Rakheja D, Li Q, Mohan C, Clayberger C, Wakeland E, Khan S. KLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes. Communications Biology 2024, 7: 1446. PMID: 39506084, PMCID: PMC11541912, DOI: 10.1038/s42003-024-07099-0.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusMyeloid cellsLupus nephritisT cellsKidneys of lupus-prone miceSystemic lupus erythematosus pathogenesisLevels of proinflammatory cytokinesLupus-prone miceActivated myeloid cellsActivated T cellsT cell activationProduction of RANTEST cell hyperactivityProinflammatory cytokine genesAssociated with increased productionLupus pathogenesisProinflammatory cytokines/chemokinesSle1 locusLupus erythematosusImmune activationProinflammatory cytokinesCytokine signaling pathwaysCytokine genesGenome-wide transcriptional changesReceptor ligandsSomatic mosaicism in schizophrenia brains reveals prenatal mutational processes
Maury E, Jones A, Seplyarskiy V, Nguyen T, Rosenbluh C, Bae T, Wang Y, Abyzov A, Khoshkhoo S, Chahine Y, Zhao S, Venkatesh S, Root E, Voloudakis G, Roussos P, Network B, Park P, Akbarian S, Brennand K, Reilly S, Lee E, Sunyaev S, Walsh C, Chess A. Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes. Science 2024, 386: 217-224. PMID: 39388546, PMCID: PMC11490355, DOI: 10.1126/science.adq1456.Peer-Reviewed Original ResearchConceptsTranscription factor binding sitesWhole-genome sequencingOpen chromatinMutational processesSomatic mutationsFactor binding sitesSchizophrenia casesSchizophrenia risk genesSomatic mosaicismSomatic variantsRisk genesG mutationGene expressionGermline mutationsBinding sitesGenesMutationsIncreased somatic mutationsChromatinMosaic somatic mutationsPrenatal neurogenesisContext of schizophreniaBrain neuronsSchizophrenia brainVariantsAn RNA-centric view of transcription and genome organization
Henninger J, Young R. An RNA-centric view of transcription and genome organization. Molecular Cell 2024, 84: 3627-3643. PMID: 39366351, PMCID: PMC11495847, DOI: 10.1016/j.molcel.2024.08.021.Peer-Reviewed Original ResearchConceptsGene regulationGenome architectureTranscriptional regulationModel of transcriptional regulationAssembly of protein complexesAssembly of transcription complexesLocal genome architectureSilencing of genesGenomic compartmentsGenome organizationGenomic structureRNA polymeraseChromatin regulationTranscription complexActive genesProtein complexesRNA moleculesTranscription factorsGenomeProtein kinaseSpecific genesGenesFeedback regulationRNASpatial compartmentsA cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders
Lee A, Ayers L, Kosicki M, Chan W, Fozo L, Pratt B, Collins T, Zhao B, Rose M, Sanchis-Juan A, Fu J, Wong I, Zhao X, Tenney A, Lee C, Laricchia K, Barry B, Bradford V, Jurgens J, England E, Lek M, MacArthur D, Lee E, Talkowski M, Brand H, Pennacchio L, Engle E. A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders. Nature Communications 2024, 15: 8268. PMID: 39333082, PMCID: PMC11436875, DOI: 10.1038/s41467-024-52463-7.Peer-Reviewed Original ResearchConceptsNon-coding variantsCranial motor neuronsMendelian disordersIn vivo transgenic assayPredictor of enhancer activityCis-regulatory elementsMulti-omic frameworkWhole-genome sequencingEnhanced activityVariant discoveryGenome sequenceChromatin accessibilityPutative enhancersHistone modificationsRegulatory elementsGene expression assaysGene predictionTransgenic assaysEpigenomic profilingMendelian casesExpression assaysMutational enhancementCongenital cranial dysinnervation disordersCell typesFunctional impactContext-aware single-cell multiomics approach identifies cell-type-specific lung cancer susceptibility genes
Long E, Yin J, Shin J, Li Y, Li B, Kane A, Patel H, Sun X, Wang C, Luong T, Xia J, Han Y, Byun J, Zhang T, Zhao W, Landi M, Rothman N, Lan Q, Chang Y, Yu F, Amos C, Shi J, Lee J, Kim E, Choi J. Context-aware single-cell multiomics approach identifies cell-type-specific lung cancer susceptibility genes. Nature Communications 2024, 15: 7995. PMID: 39266564, PMCID: PMC11392933, DOI: 10.1038/s41467-024-52356-9.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide association study lociSusceptibility genesLung cancer susceptibility genesTranscription factor footprintsChromatin accessibility mapsCis-regulatory elementsRisk-associated variantsRare cell typesRegulate gene expressionCell typesCell type-specificCancer susceptibility genesCausal variantsAssociation studiesGene regulationGene functionMultiomics approachTarget genesLociGene expressionGenesType-specificHuman lung cellsCCREsAn autoimmune transcriptional circuit drives FOXP3+ regulatory T cell dysfunction
Sumida T, Lincoln M, He L, Park Y, Ota M, Oguchi A, Son R, Yi A, Stillwell H, Leissa G, Fujio K, Murakawa Y, Kulminski A, Epstein C, Bernstein B, Kellis M, Hafler D. An autoimmune transcriptional circuit drives FOXP3+ regulatory T cell dysfunction. Science Translational Medicine 2024, 16: eadp1720. PMID: 39196959, DOI: 10.1126/scitranslmed.adp1720.Peer-Reviewed Original ResearchConceptsForkhead box P3Autoimmune diseasesCD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T cellsMultiple sclerosisFoxp3<sup>+</sup> regulatory T cellsRegulatory T cell dysfunctionPR domain zinc finger protein 1Zinc finger protein 1Glucocorticoid-regulated kinase 1Regulatory T cellsT cell dysfunctionDisorder of young adultsAutoimmune disease multiple sclerosisDisease multiple sclerosisExpression of serumTranscriptional circuitsEpigenomic profilingShort isoformPrevent autoimmunityUpstream regulatorT cellsHuman autoimmunityEvolutionary emergenceKinase 1Molecular mechanismsACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses
Kaymak I, Watson M, Oswald B, Ma S, Johnson B, DeCamp L, Mabvakure B, Luda K, H. E, Lau K, Fu Z, Muhire B, Kitchen-Goosen S, Vander Ark A, Dahabieh M, Samborska B, Vos M, Shen H, Fan Z, Roddy T, Kingsbury G, Sousa C, Krawczyk C, Williams K, Sheldon R, Kaech S, Roy D, Jones R. ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses. Journal Of Experimental Medicine 2024, 221: e20231820. PMID: 39150482, PMCID: PMC11329787, DOI: 10.1084/jem.20231820.Peer-Reviewed Original ResearchConceptsAcyl-CoA synthetase short-chain family member 2Acetyl-CoA productionATP citrate lyaseChromatin accessibilityAcetyl-CoAEnzyme ATP citrate lyaseFamily member 2Function in vivoCoordination of cellular metabolismTCA cycleMetabolic nodesGene locusCitrate lyaseT cell effector responsesHistone acetylationCellular metabolismEffector functionsCD8 T cellsResponse to infectionMember 2ChromatinEffector responsesMetabolic substratesT cell response to infectionT cellsIdentifying 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 ResearchMeSH KeywordsAlgorithmsAnimalsChromatinComputational BiologyHumansImage Processing, Computer-AssistedConceptsTopologically 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 techniquesBACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells
Thakore P, Schnell A, Huang L, Zhao M, Hou Y, Christian E, Zaghouani S, Wang C, Singh V, Singaraju A, Krishnan R, Kozoriz D, Ma S, Sankar V, Notarbartolo S, Buenrostro J, Sallusto F, Patsopoulos N, Rozenblatt-Rosen O, Kuchroo V, Regev A. BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells. Nature Immunology 2024, 25: 1395-1410. PMID: 39009838, DOI: 10.1038/s41590-024-01901-1.Peer-Reviewed Original ResearchConceptsTransposase-accessible chromatin sequencingSingle-cell RNA sequencingTh17 heterogeneitySingle-cell assaysScATAC-seqChromatin landscapeChromatin stateChromatin sequencingRegulatory networksScRNA-seqTh17 cell pathogenicityHuman geneticsIn vivoRNA sequencingChromatin configurationRegulatory pathwaysTissue homeostasisCell statesCells in vitroBach2ChromatinSequenceCellsType 1 helper T (Th1) cellsCD4+ T cell subsetsSingle-cell genomics and regulatory networks for 388 human brains
Emani P, Liu J, Clarke D, Jensen M, Warrell J, Gupta C, Meng R, Lee C, Xu S, Dursun C, Lou S, Chen Y, Chu Z, Galeev T, Hwang A, Li Y, Ni P, Zhou X, Bakken T, Bendl J, Bicks L, Chatterjee T, Cheng L, Cheng Y, Dai Y, Duan Z, Flaherty M, Fullard J, Gancz M, Garrido-Martín D, Gaynor-Gillett S, Grundman J, Hawken N, Henry E, Hoffman G, Huang A, Jiang Y, Jin T, Jorstad N, Kawaguchi R, Khullar S, Liu J, Liu J, Liu S, Ma S, Margolis M, Mazariegos S, Moore J, Moran J, Nguyen E, Phalke N, Pjanic M, Pratt H, Quintero D, Rajagopalan A, Riesenmy T, Shedd N, Shi M, Spector M, Terwilliger R, Travaglini K, Wamsley B, Wang G, Xia Y, Xiao S, Yang A, Zheng S, Gandal M, Lee D, Lein E, Roussos P, Sestan N, Weng Z, White K, Won H, Girgenti M, Zhang J, Wang D, Geschwind D, Gerstein M, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Berretta S, Bharadwaj R, Bhattacharya A, Brennand K, Capauto D, Champagne F, Chatzinakos C, Chen H, Cheng L, Chess A, Chien J, Clement A, Collado-Torres L, Cooper G, Crawford G, Dai R, Daskalakis N, Davila-Velderrain J, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duong D, Eagles N, Edelstein J, Galani K, Girdhar K, Goes F, Greenleaf W, Guo H, Guo Q, Hadas Y, Hallmayer J, Han X, Haroutunian V, He C, Hicks S, Ho M, Ho L, Huang Y, Huuki-Myers L, Hyde T, Iatrou A, Inoue F, Jajoo A, Jiang L, Jin P, Jops C, Jourdon A, Kellis M, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Li J, Li M, Lin X, Liu S, Liu C, Loupe J, Lu D, Ma L, Mariani J, Martinowich K, Maynard K, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Mukamel E, Nairn A, Nemeroff C, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Pinto D, Pochareddy S, Pollard K, Pollen A, Przytycki P, Purmann C, Qin Z, Qu P, Raj T, Reach S, Reimonn T, Ressler K, Ross D, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Seyfried N, Shao Z, Shieh A, Shin J, Skarica M, Snijders C, Song H, State M, Stein J, Steyert M, Subburaju S, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, Voloudakis G, Wang T, Wang S, Wang Y, Wei Y, Weimer A, Weinberger D, Wen C, Whalen S, Willsey A, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang Y, Ziffra R, Zeier Z, Zintel T. Single-cell genomics and regulatory networks for 388 human brains. Science 2024, 384: eadi5199. PMID: 38781369, PMCID: PMC11365579, DOI: 10.1126/science.adi5199.Peer-Reviewed Original ResearchConceptsSingle-cell genomicsSingle-cell expression quantitative trait locusExpression quantitative trait lociDrug targetsQuantitative trait lociPopulation-level variationSingle-cell expressionCell typesDisease-risk genesTrait lociGene familyRegulatory networksGene expressionCell-typeMultiomics datasetsSingle-nucleiGenomeGenesCellular changesHeterogeneous tissuesExpressionCellsChromatinLociMultiomicsMassively parallel characterization of regulatory elements in the developing human cortex
Deng C, Whalen S, Steyert M, Ziffra R, Przytycki P, Inoue F, Pereira D, Capauto D, Norton S, Vaccarino F, Pollen A, Nowakowski T, Ahituv N, Pollard K, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Bendl J, Berretta S, Bharadwaj R, Bhattacharya A, Bicks L, Brennand K, Capauto D, Champagne F, Chatterjee T, Chatzinakos C, Chen Y, Chen H, Cheng Y, Cheng L, Chess A, Chien J, Chu Z, Clarke D, Clement A, Collado-Torres L, Cooper G, Crawford G, Dai R, Daskalakis N, Davila-Velderrain J, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duan Z, Duong D, Dursun C, Eagles N, Edelstein J, Emani P, Fullard J, Galani K, Galeev T, Gandal M, Gaynor S, Gerstein M, Geschwind D, Girdhar K, Goes F, Greenleaf W, Grundman J, Guo H, Guo Q, Gupta C, Hadas Y, Hallmayer J, Han X, Haroutunian V, Hawken N, He C, Henry E, Hicks S, Ho M, Ho L, Hoffman G, Huang Y, Huuki-Myers L, Hwang A, Hyde T, Iatrou A, Inoue F, Jajoo A, Jensen M, Jiang L, Jin P, Jin T, Jops C, Jourdon A, Kawaguchi R, Kellis M, Khullar S, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Lee C, Lee D, Li J, Li M, Lin X, Liu S, Liu J, Liu J, Liu C, Liu S, Lou S, Loupe J, Lu D, Ma S, Ma L, Margolis M, Mariani J, Martinowich K, Maynard K, Mazariegos S, Meng R, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Moore J, Moran J, Mukamel E, Nairn A, Nemeroff C, Ni P, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Phalke N, Pinto D, Pjanic M, Pochareddy S, Pollard K, Pollen A, Pratt H, Przytycki P, Purmann C, Qin Z, Qu P, Quintero D, Raj T, Rajagopalan A, Reach S, Reimonn T, Ressler K, Ross D, Roussos P, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Sestan N, Seyfried N, Shao Z, Shedd N, Shieh A, Shin J, Skarica M, Snijders C, Song H, State M, Stein J, Steyert M, Subburaju S, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, Voloudakis G, Wamsley B, Wang T, Wang S, Wang D, Wang Y, Warrell J, Wei Y, Weimer A, Weinberger D, Wen C, Weng Z, Whalen S, White K, Willsey A, Won H, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Xu S, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang J, Zhang Y, Zhou X, Ziffra R, Zeier Z, Zintel T. Massively parallel characterization of regulatory elements in the developing human cortex. Science 2024, 384: eadh0559. PMID: 38781390, DOI: 10.1126/science.adh0559.Peer-Reviewed Original ResearchConceptsGene regulatory elementsRegulatory elementsRegulation of enhancer activityCharacterization of regulatory elementsCis-regulatory activityNeuronal developmentPrimary cellsEnhanced activityGene regulationHuman neuronal developmentNucleotide changesEnhancer sequencesSequence basisUpstream regulatorComprehensive catalogHuman cellsDeveloping cortexSequenceVariantsOrganoidsCellsCerebral organoidsCortexHuman cortexNucleotideEffect 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 simulationsGenetic drivers of heterogeneity in type 2 diabetes pathophysiology
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Saotome M, Poduval D, Grimm S, Nagornyuk A, Gunarathna S, Shimbo T, Wade P, Takaku M. Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4. Nucleic Acids Research 2024, 52: 3607-3622. PMID: 38281186, PMCID: PMC11039999, DOI: 10.1093/nar/gkae025.Peer-Reviewed Original ResearchConceptsTranscription factorsBreast cancer cellsBinding motifTranscription factor binding motifsTranscription factor-DNA interactionsLineage-determining transcription factorsCellular reprogrammingProof-reading enzymeBasal breast cancer cellsChromatin-binding activityCancer cellsBinding site selectionEukaryotic genomesNucleosome positioningChromatin accessibilityChromatin openingGene activationCHD4Gene expressionChromatinTranscriptionBinding activityFrequent mutationsUnoccupied sitesExquisite specificity
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