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MiOS_an_integrated_imaging.pdf (17.78 MB)

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2022-10-11

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/192014

MiOS, an integrated imaging and computational strategy to model gene folding with nucleosome resolution

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https://doi.org/10.1038/s41594-022-00839-y

Resum

The linear sequence of DNA provides invaluable information about genes and their regulatory elements along chromosomes. However, to fully understand gene function and regulation, we need to dissect how genes physically fold in the three-dimensional nuclear space. Here we describe immuno-OligoSTORM, an imaging strategy that reveals the distribution of nucleosomes within specific genes in super-resolution, through the simultaneous visualization of DNA and histones. We combine immuno-OligoSTORM with restraint-based and coarse-grained modeling approaches to integrate super-resolution imaging data with Hi-C contact frequencies and deconvoluted micrococcal nuclease-sequencing information. The resulting method, called Modeling immuno-OligoSTORM, allows quantitative modeling of genes with nucleosome resolution and provides information about chromatin accessibility for regulatory factors, such as RNA polymerase II. With Modeling immuno-OligoSTORM, we explore intercellular variability, transcriptional-dependent gene conformation, and folding of housekeeping and pluripotency-related genes in human pluripotent and differentiated cells, thereby obtaining the highest degree of data integration achieved so far to our knowledge.

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Genòmica, Genètica molecular, Gens

Matèries (anglès)

Genomics, Molecular genetics, Genes

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

NEGUEMBOR, Maria victoria, ARCON, Juan pablo, BUITRAGO OSPINA, Diana camila, LEMA, Rafael, WALTHER, Jürgen, GARATE, Ximena, MARTÍN DE DIOS, Laura, ROMERO, Pablo, ALHAJ ABED, Juman, GUT, Marta, BLANC, Julie, LAKADAMYALI, Melike, WU, Chao-ting, BRUN HEATH, Isabelle, OROZCO LÓPEZ, Modesto, DANS, Pablo d., PIA COSMA, Maria. MiOS, an integrated imaging and computational strategy to model gene folding with nucleosome resolution. _Nature Structural & Molecular Biology_. 2022. Vol. 29, núm. 10, pàgs. 1011–1023. [consulta: 29 de gener de 2026]. ISSN: 1545-9985. [Disponible a: https://hdl.handle.net/2445/192014]

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