Transcription-mediated supercoiling regulates genome folding and loop formation
| العنوان: | Transcription-mediated supercoiling regulates genome folding and loop formation |
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| المؤلفون: | Maria Victoria Neguembor, Chao-ting Wu, Maria Pia Cosma, Chiara Vicario, Pablo Aurelio Gómez-García, Laura Martin, Álvaro Castells-García, Melike Lakadamyali, Francesco Sottile, Davide Carnevali, Jumana AlHaj Abed, Jérôme Solon, Ruben Sebastian-Perez, Alba Granados |
| المساهمون: | European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat de Catalunya, National Natural Science Foundation of China, Guangzhou Institute of Science and Technology, University of Pennsylvania, National Science Foundation (US), National Institutes of Health (US), Fundación 'la Caixa' |
| المصدر: | Molecular cell. 81(15) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Transcription, Genetic, Supercoiling, Chromosomal Proteins, Non-Histone, STORM microscopy, RNA polymerase II, Cell Cycle Proteins, Cell Line, chemistry.chemical_compound, Prophase, Transcription (biology), Humans, Super-resolution microscopy, Molecular Biology, Chromatin Fiber, Cohesin, Cell Nucleus, biology, Cell Biology, Chromatin, Lamins, Single Molecule Imaging, Cell biology, DNA-Binding Proteins, chemistry, Chondroitin Sulfate Proteoglycans, DNA Topoisomerases, Type I, biology.protein, Genome folding, DNA supercoil, Female, RNA Polymerase II, biological phenomena, cell phenomena, and immunity, Transcription, DNA |
| الوصف: | The chromatin fiber folds into loops, but the mechanisms controlling loop extrusion are still poorly understood. Using super-resolution microscopy, we visualize that loops in intact nuclei are formed by a scaffold of cohesin complexes from which the DNA protrudes. RNA polymerase II decorates the top of the loops and is physically segregated from cohesin. Augmented looping upon increased loading of cohesin on chromosomes causes disruption of Lamin at the nuclear rim and chromatin blending, a homogeneous distribution of chromatin within the nucleus. Altering supercoiling via either transcription or topoisomerase inhibition counteracts chromatin blending, increases chromatin condensation, disrupts loop formation, and leads to altered cohesin distribution and mobility on chromatin. Overall, negative supercoiling generated by transcription is an important regulator of loop formation in vivo. e acknowledge support from European Union’s Horizon 2020 research and innovation program (CellViewer 686637 to J.S., M.L., and M.P.C.); Ministerio de Ciencia e Innovación (grant BFU2017-86760-P [AEI/FEDER, UE] to M.P.C.), and an AGAUR grant from Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya (2017 SGR 689 to M.P.C.); Centro de Excelencia Severo Ochoa (2013–2017 to M.P.C.); CERCA Programme/Generalitat de Catalunya (to M.P.C.); the Spanish Ministry of Science and Innovation to the European Molecular Biology Laboratory (EMBL) partnership (to M.P.C.); the National Natural Science Foundation of China (31971177 to M.P.C.); the Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR110103001 to M.P.C.); a Linda Pechenik Montague Investigator Award (to M.L.); a University of Pennsylvania Epigenetics Pilot Award (to M.L.); the Center for Engineering and Mechanobiology (CEMB) a National Science Foundation (NSF) Science and Technology Center Pilot Award (Division of Civil, Mechanical and Manufacturing Innovation [CMMI]: 15-48571 to M.L.); NIH grants R01HD091797 and R01GM123289 (to C.t.W.); the People Program (Marie Skłodowska-Curie Actions) FP7/2007–2013 under an REA grant (608959 to M.V.N.); Juan de la Cierva-Incorporación 2017 (to M.V.N.); Grant for the recruitment of early-stage research staff FI-2020 (Operational Program of Catalonia 2014–2020 CCI 2014ES05SFOP007 of the European Social Fund to L.M.); a “la Caixa” Foundation Fellowship (ID 100010434, LCF/BQ/DR20/11790016) (to L.M.); “La Caixa-Severo Ochoa” pre-doctoral fellowship (to Á.C.-G.); and Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya and the co-financing of Fondo Social Europeo (2018FI_B_00637 and FSE to R.S.-P.), and a La Caixa international PhD fellowship (to F.S.). |
| وصف الملف: | application/pdf |
| تدمد: | 1097-4164 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1023dbcf3cf0c90ca245d39ee9591798 https://pubmed.ncbi.nlm.nih.gov/34358457 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1023dbcf3cf0c90ca245d39ee9591798 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974164 |
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