2024
Functional Roles of H3K4 Methylation in Transcriptional Regulation
Yu H, Lesch B. Functional Roles of H3K4 Methylation in Transcriptional Regulation. Molecular And Cellular Biology 2024, 44: 505-515. PMID: 39155435, PMCID: PMC11529435, DOI: 10.1080/10985549.2024.2388254.Peer-Reviewed Original ResearchTranscriptional regulationAssociated with active transcriptionHistone 3 lysine 4 methylationFunctional roleTranscribed lociOpen chromatinActivate transcriptionChromatin modificationsH3K4 methylationRegulatory elementsHistone methyltransferaseEpigenetic editingTranscriptional activityResidue mutationsMammalian systemsCell differentiationHistoneH3K4me1H3K4meH3K4me3ChromatinRegulationH3K4YeastLoci
2023
Human-specific epigenomic states in spermatogenesis
Liao C, Walters B, DiStasio M, Lesch B. Human-specific epigenomic states in spermatogenesis. Computational And Structural Biotechnology Journal 2023, 23: 577-588. PMID: 38274996, PMCID: PMC10809009, DOI: 10.1016/j.csbj.2023.12.037.Peer-Reviewed Original ResearchKDM6A/UTX promotes spermatogenic gene expression across generations and is not required for male fertility†
Walters B, Rainsford S, Heuer R, Dias N, Huang X, de Rooij D, Lesch B. KDM6A/UTX promotes spermatogenic gene expression across generations and is not required for male fertility†. Biology Of Reproduction 2023, 110: 391-407. PMID: 37861693, PMCID: PMC11484508, DOI: 10.1093/biolre/ioad141.Peer-Reviewed Original ResearchMale germ lineGerm lineGenome-wide epigenetic profilingGene regulatory statesHeritable epigenetic statesHundreds of genesLoss of KDM6AEarly meiotic prophaseSpermatogenic cellsSpermatogenic gene expressionKDM6A/UTXPaternal germ lineDemethylation of H3K27me3H3K27me3 peaksH3K27me3 domainsMisregulated genesEpigenetic stateChromatin organizationRepressive modificationsTranscriptional activatorMammalian spermatogenesisChromatin undergoesLysine demethylase 6AEpigenetic profilingGene activationANALYSIS OF INTER-INDIVIDUAL VARIATION IN CHROMATIN BIVALENCY IN THE HUMAN MALE GERM LINE
Heuer R, Ayaz A, Seli E, Lesch B. ANALYSIS OF INTER-INDIVIDUAL VARIATION IN CHROMATIN BIVALENCY IN THE HUMAN MALE GERM LINE. Fertility And Sterility 2023, 120: e219-e220. DOI: 10.1016/j.fertnstert.2023.08.629.Peer-Reviewed Original ResearchDOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres
Malla A, Yu H, Farris D, Kadimi S, Lam T, Cox A, Smith Z, Lesch B. DOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres. EMBO Reports 2023, 24: e56492. PMID: 37317657, PMCID: PMC10398668, DOI: 10.15252/embr.202256492.Peer-Reviewed Original ResearchConceptsMouse embryonic stem cellsBurst of transcriptionMajor satellite repeatsLong-term silencingRepetitive DNA elementsEmbryonic stem cellsSatellite transcriptionHeterochromatin stabilityHeterochromatin formationHeterochromatin structureChromatin stateSatellite repeatsGenome stabilityGenome integrityPericentromeric repeatsPericentromeric heterochromatinGenome featuresDNA elementsHistone H3Transcriptional activationHistone methyltransferaseRepetitive elementsDOT1L lossRepeat elementsTranscript productionDOT1L 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
Deconvolution of in vivo protein-RNA contacts using fractionated eCLIP-seq
Biancon G, Busarello E, Joshi P, Lesch B, Halene S, Tebaldi T. Deconvolution of in vivo protein-RNA contacts using fractionated eCLIP-seq. STAR Protocols 2022, 3: 101823. PMID: 36595959, PMCID: PMC9676202, DOI: 10.1016/j.xpro.2022.101823.Peer-Reviewed Original ResearchConceptsProtein-RNA interactionsIndividual RNA-binding proteinsTranscriptome-wide analysisThousands of RNAsProtein-RNA contactsRNA-binding proteinSingle nucleotide levelComputational analysis pipelineRNA processingMulticomponent complexesRNA immunoprecipitationRead countsComplete detailsAnalysis pipelineAdditional levelProteinImmunoprecipitationRNAInteractionComplexesWidespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction
Griffin KN, Walters BW, Li H, Wang H, Biancon G, Tebaldi T, Kaya CB, Kanyo J, Lam TT, Cox AL, Halene S, Chung JJ, Lesch BJ. Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction. Genome Research 2022, 32: 1655-1668. PMID: 36109149, PMCID: PMC9528986, DOI: 10.1101/gr.276578.122.Peer-Reviewed Original ResearchMammalian male reproductionArgonaute 2Distinct nuclear functionsConditional knockoutMale reproductionProtein Argonaute 2Abnormal sperm head morphologyMeiotic chromatinAnimal developmentCytoplasmic roleNuclear functionsMale meiosisNuclear roleMRNA translationAgo2 proteinImportant genesNuclear compartmentMRNA transcriptsBiological relevanceSperm head morphologyHead morphologySpermatogenic cellsWidespread associationChromatinProtein
2021
Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions
Chandrasekaran S, Espeso-Gil S, Loh YE, Javidfar B, Kassim B, Zhu Y, Zhang Y, Dong Y, Bicks LK, Li H, Rajarajan P, Peter CJ, Sun D, Agullo-Pascual E, Iskhakova M, Estill M, Lesch BJ, Shen L, Jiang Y, Akbarian S. Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions. Nature Communications 2021, 12: 7243. PMID: 34903713, PMCID: PMC8669064, DOI: 10.1038/s41467-021-26862-z.Peer-Reviewed Original ResearchConceptsCellular stress response genesOpen chromatin domainsChromatin domain organizationRepeat-rich sequencesStress response genesRetrotransposon expansionsSPRET/EiJChromatin domainsChromosomal architectureChromosomal conformationDomain organizationAdult mouse cerebral cortexMurine germlineTranscriptional dysregulationResponse genesRegulatory mechanismsMus musculusMature neuronsNeuronal ablationStrong enrichmentMouse cerebral cortexSequenceSETDB1Single moleculesGermlineEpigenetic states in the human placenta: A singular epigenome for an exceptional tissue
Lesch BJ. Epigenetic states in the human placenta: A singular epigenome for an exceptional tissue. Developmental Cell 2021, 56: 1211-1212. PMID: 33945779, DOI: 10.1016/j.devcel.2021.04.011.Commentaries, Editorials and Letters
2020
H3K4me1 Distribution Predicts Transcription State and Poising at Promoters
Bae S, Lesch BJ. H3K4me1 Distribution Predicts Transcription State and Poising at Promoters. Frontiers In Cell And Developmental Biology 2020, 8: 289. PMID: 32432110, PMCID: PMC7214686, DOI: 10.3389/fcell.2020.00289.Peer-Reviewed Original ResearchGerm cellsGene regulatory statesDifferent epigenetic marksTranscription start siteEmbryonic stem cellsMouse germ cellsGene expression levelsTranscription stateChromatin stateEpigenetic memoryEpigenetic stateEpigenetic marksLysine 4Histone H3Somatic cellsDistal enhancerStart siteActive promotersH3K4me1Transcriptional activityPromoter regionH3K4me3Possible rolePromoterCell typesSperm Go to (Transcription) Extremes
Lesch BJ. Sperm Go to (Transcription) Extremes. Cell 2020, 180: 212-213. PMID: 31978338, DOI: 10.1016/j.cell.2019.12.033.Commentaries, Editorials and Letters
2019
A universal transportin protein drives stochastic choice of olfactory neurons via specific nuclear import of a sox-2-activating factor
Alqadah A, Hsieh YW, Xiong R, Lesch BJ, Chang C, Chuang CF. A universal transportin protein drives stochastic choice of olfactory neurons via specific nuclear import of a sox-2-activating factor. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 25137-25146. PMID: 31767767, PMCID: PMC6911211, DOI: 10.1073/pnas.1908168116.Peer-Reviewed Original ResearchConceptsBK potassium channelsNuclear importUnbiased forward genetic screenSpecific nuclear importForward genetic screenCell fate choiceTranscription factor SOX-2Notch-independent mechanismStructure-function insightsPotassium channelsHigh mobility groupProtein kinase pathwayAmino acid residuesAWC asymmetryGenetic screenFunction mutantsHuman neurological disordersAWC neuronsFate choiceKinase pathwayBiological processesAcid residuesMobility groupCalcium signalingSox-2Intergenerational epigenetic inheritance of cancer susceptibility in mammals
Lesch BJ, Tothova Z, Morgan EA, Liao Z, Bronson RT, Ebert BL, Page DC. Intergenerational epigenetic inheritance of cancer susceptibility in mammals. ELife 2019, 8: e39380. PMID: 30963999, PMCID: PMC6456297, DOI: 10.7554/elife.39380.Peer-Reviewed Original ResearchConceptsGerm lineEpigenetic changesParental germ lineIntergenerational epigenetic inheritanceRegulation of genesPaternal germ lineCancer susceptibilityChromatin regulatorsEpigenetic inheritanceH3K27me3 marksHypermethylated regionsDNA methylationSomatic tissuesMale gametesElevated tumor incidenceCancer initiationGenetic variantsGermline deletionMutantsHeritabilityDeletionSuccessive generationsSpermOffspringWild-type mice
2016
Erratum: Corrigendum: Parallel evolution of male germline epigenetic poising and somatic development in animals
Lesch B, Silber S, McCarrey J, Page D. Erratum: Corrigendum: Parallel evolution of male germline epigenetic poising and somatic development in animals. Nature Genetics 2016, 48: 1296-1296. PMID: 27681290, DOI: 10.1038/ng1016-1296b.Peer-Reviewed Original ResearchParallel evolution of male germline epigenetic poising and somatic development in animals
Lesch BJ, Silber SJ, McCarrey JR, Page DC. Parallel evolution of male germline epigenetic poising and somatic development in animals. Nature Genetics 2016, 48: 888-894. PMID: 27294618, DOI: 10.1038/ng.3591.Peer-Reviewed Original Research
2014
Poised chromatin in the mammalian germ line
Lesch BJ, Page DC. Poised chromatin in the mammalian germ line. Development 2014, 141: 3619-3626. PMID: 25249456, PMCID: PMC4197577, DOI: 10.1242/dev.113027.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMammalian germ lineGerm cell identityCell identityGerm lineMammalian germ cellsEmbryonic stem cellsChromatin stateEpigenetic inheritanceHistone modificationsRegulatory genesGene activationDNA methylationEpigenetic featuresChromatinGerm cellsStem cellsSomatic developmentGenesPromoterFetal stageTotipotencyCellsMeiosisGametogenesisRepressionA Chromatin-Dependent Role of the Fragile X Mental Retardation Protein FMRP in the DNA Damage Response
Alpatov R, Lesch BJ, Nakamoto-Kinoshita M, Blanco A, Chen S, Stützer A, Armache KJ, Simon MD, Xu C, Ali M, Murn J, Prisic S, Kutateladze TG, Vakoc CR, Min J, Kingston RE, Fischle W, Warren ST, Page DC, Shi Y. A Chromatin-Dependent Role of the Fragile X Mental Retardation Protein FMRP in the DNA Damage Response. Cell 2014, 157: 869-881. PMID: 24813610, PMCID: PMC4038154, DOI: 10.1016/j.cell.2014.03.040.Peer-Reviewed Original ResearchConceptsDNA damage responseMental retardation protein FMRPProtein FMRPFragile X syndromeDDR machineryDamage responseChromatin-binding proteinsTandem Tudor domainTranslation of proteinsX syndromeChromatin interfaceFMRP bindsTudor domainMeiotic chromosomesGenomic stabilityFMRPDevelopmental processesMouse spermatogenesisGametogenesisDependent mannerSynaptic functionMachineryProteinChromatinImportant role
2013
A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis
Lesch BJ, Dokshin GA, Young RA, McCarrey JR, Page DC. A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 16061-16066. PMID: 24043772, PMCID: PMC3791702, DOI: 10.1073/pnas.1315204110.Peer-Reviewed Original ResearchConceptsSet of genesGerm cellsPostmeiotic male germ cellsGerm line nucleiSexual differentiationRNA-seq analysisFemale germ cellsSubset of genesEmbryonic stem cellsMale germ cellsRegulators of differentiationEnd of meiosisCompletion of meiosisMouse germ cellsTotipotent zygoteDifferentiated gametesMulticellular organismsGamete precursorsDevelopmental genesChIP-seqGerm lineGamete unionExtraembryonic tissuesMeiotic initiationPostmeiotic cellsThe Ligand Binding Domain of GCNF Is Not Required for Repression of Pluripotency Genes in Mouse Fetal Ovarian Germ Cells
Okumura LM, Lesch BJ, Page DC. The Ligand Binding Domain of GCNF Is Not Required for Repression of Pluripotency Genes in Mouse Fetal Ovarian Germ Cells. PLOS ONE 2013, 8: e66062. PMID: 23762465, PMCID: PMC3676325, DOI: 10.1371/journal.pone.0066062.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDown-RegulationExonsFemaleFetusGene Expression Regulation, DevelopmentalGene TargetingGerm CellsHomeodomain ProteinsLigandsMeiosisMiceMice, Inbred C57BLMice, Mutant StrainsMutationNanog Homeobox ProteinNuclear Receptor Subfamily 6, Group A, Member 1Octamer Transcription Factor-3OogenesisOvaryPhenotypePluripotent Stem CellsProtein BindingProtein Structure, TertiarySequence DeletionStructure-Activity RelationshipConceptsFetal ovarian germ cellsOvarian germ cellsPluripotency genesSomatic cellsGerm cellsSilencing of Oct4Initiation of meiosisEmbryonic stem cellsLigand binding domainsGCNF geneEmbryonic day 14.5Tamoxifen-inducible CreDifferent developmental timepointsBinding domainsDifferentiated stateGCNFDevelopmental timepointsNanogGenesConditional ablationStem cellsDay 14.5CellsExpressionE8.0