2023
Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
de Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, PMCID: PMC10957226, DOI: 10.1016/j.ccell.2023.07.005.Peer-Reviewed Original ResearchConceptsMammalian SWI/SNF chromatinSWI/SNF chromatinMSWI/SNF complexesGenome-wide localizationGene regulatory signaturesNon-genetic mechanismsEpithelial cell differentiationEGFR-mutant cellsChromatin accessibilitySNF complexCellular programsRegulatory signaturesTKI-resistant lung cancerGene targetsKinase inhibitor resistanceCell differentiationMesenchymal transitionTKI resistancePharmacologic disruptionTyrosine kinase inhibitor resistanceCell proliferationChromatinInhibitor resistanceEGFR-mutant lungKinase inhibitorsPharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
Wei J, Patil A, Collings C, Alfajaro M, Liang Y, Cai W, Strine M, Filler R, DeWeirdt P, Hanna R, Menasche B, Ökten A, Peña-Hernández M, Klein J, McNamara A, Rosales R, McGovern B, Luis Rodriguez M, García-Sastre A, White K, Qin Y, Doench J, Yan Q, Iwasaki A, Zwaka T, Qi J, Kadoch C, Wilen C. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nature Genetics 2023, 55: 471-483. PMID: 36894709, PMCID: PMC10011139, DOI: 10.1038/s41588-023-01307-z.Peer-Reviewed Original ResearchConceptsMSWI/SNF complexesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionHost-directed therapeutic targetSyndrome coronavirus 2 infectionSARS-CoV-2 infectionSWItch/Sucrose Non-Fermentable (SWI/SNF) chromatinSARS-CoV-2 susceptibilityNon-fermentable (SWI/SNF) chromatinCoronavirus 2 infectionEnzyme 2 (ACE2) expressionSARS-CoV-2 variantsHuman cell typesPrimary human cell typesAirway epithelial cellsDrug-resistant variantsNew drug targetsChromatin accessibilitySNF complexACE2 locusACE2 expressionFactor complexHost determinantsTherapeutic targetConfer resistance
2022
Loss of PBRM1 alters promoter histone modifications and activates ALDH1A1 to drive renal cell carcinomaPBRM1 loss increases H3K4me3 marks and expression of ALDH1A1
Schoenfeld D, Zhou R, Zairis S, Su W, Steinbach N, Mathur D, Bansal A, Zachem A, Tavarez B, Hasson D, Bernstein E, Rabadan R, Parsons R. Loss of PBRM1 alters promoter histone modifications and activates ALDH1A1 to drive renal cell carcinomaPBRM1 loss increases H3K4me3 marks and expression of ALDH1A1. Molecular Cancer Research 2022, 20: 1193-1207. PMID: 35412614, PMCID: PMC9357026, DOI: 10.1158/1541-7786.mcr-21-1039.Peer-Reviewed Original ResearchConceptsRetinoic acid biosynthesisSuch target genesPromoter histone modificationsAcid biosynthesisHistone modificationsClear cell renal cell carcinomaTarget genesLoss of PBRM1SWI/SNF complexSWI/SNF chromatinSWI/SNF subunitsHistone modification ChIP-seqSWI/SNF componentsATAC-seq dataCcRCC cell linesDe novo gainPBAF subunitsH3K4me3 peaksH3K4me3 marksPBAF complexSNF complexEpigenomic approachesChIP-seqRNA-seqHigh mutation frequency
2014
Evidence for Chromatin-Remodeling Complex PBAP-Controlled Maintenance of the Drosophila Ovarian Germline Stem Cells
He J, Xuan T, Xin T, An H, Wang J, Zhao G, Li M. Evidence for Chromatin-Remodeling Complex PBAP-Controlled Maintenance of the Drosophila Ovarian Germline Stem Cells. PLOS ONE 2014, 9: e103473. PMID: 25068272, PMCID: PMC4113433, DOI: 10.1371/journal.pone.0103473.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedCell Cycle ProteinsCell DifferentiationChromatin Assembly and DisassemblyChromosomal Proteins, Non-HistoneDrosophila melanogasterDrosophila ProteinsFemaleGene ExpressionGreen Fluorescent ProteinsMicroscopy, ConfocalMutationOvaryOvumProtein BindingReverse Transcriptase Polymerase Chain ReactionRNA InterferenceTrans-ActivatorsTranscription FactorsConceptsGermline stem cellsGermline differentiationFate regulationDrosophila ovarian germline stem cellsSWI/SNF chromatin-remodeling complexOvarian germline stem cellsSWI/SNF complexStem cell fate regulationComplex-specific subunitsChromatin-remodeling complexCell fate regulationGenetic interaction testsStem cellsGSC fateGSC lossBAP complexDrosophila oogenesisMutant phenotypeSNF complexGSC maintenanceBRM functionRegulatory machineryEpigenetic regulationProtein complexesATPase subunits
2002
Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes
Chi TH, Wan M, Zhao K, Taniuchi I, Chen L, Littman DR, Crabtree GR. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature 2002, 418: 195-199. PMID: 12110891, DOI: 10.1038/nature00876.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4 AntigensCD8 AntigensChromatinCross-Linking ReagentsDNA HelicasesDNA-Binding ProteinsFlow CytometryGene Expression RegulationGene SilencingMacromolecular SubstancesMiceMice, TransgenicMutationNuclear ProteinsProtein BindingProtein Structure, TertiaryProtein SubunitsThymus GlandTranscription FactorsConceptsBAF complexCD4 silencerYeast SWI/SNF complexSWI/SNF-like BAF complexHigh mobility group domainSWI/SNF complexLineage-specific genesDNA-binding subunitLineage bifurcationChromatin remodellingHMG domainChromatin lociSNF complexDNA bendingReciprocal regulationGroup domainCD4/CD8 expressionCell killingThymic developmentSilencerMutationsComplexesExpressionBAF57BRG
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