How chromosome topologies get their shape: views from proximity ligation and microscopy methods

Yike Huang, Roel Neijts, Wouter de Laat

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveBoek/film/artikelrecensieWetenschappelijk

Samenvatting

The 3D organization of our genome is an important determinant for the transcriptional output of a gene in (patho)physiological contexts. The spatial organization of linear chromosomes within nucleus is dominantly inferred using two distinct approaches, chromosome conformation capture (3C) and DNA fluorescent in situ hybridization (DNA-FISH). While 3C and its derivatives score genomic interaction frequencies based on proximity ligation events, DNA-FISH methods measure physical distances between genomic loci. Despite these approaches probe different characteristics of chromosomal topologies, they provide a coherent picture of how chromosomes are organized in higher-order structures encompassing chromosome territories, compartments, and topologically associating domains. Yet, at the finer topological level of promoter-enhancer communication, the imaging-centered and the 3C methods give more divergent and sometimes seemingly paradoxical results. Here, we compare and contrast observations made applying visual DNA-FISH and molecular 3C approaches. We emphasize that the 3C approach, due to its inherently competitive ligation step, measures only 'relative' proximities. A 3C interaction enriched between loci, therefore does not necessarily translates into a decrease in absolute spatial distance. Hence, we advocate caution when modeling chromosome conformations.

Originele taal-2Engels
Pagina's (van-tot)3439-3449
Aantal pagina's11
TijdschriftFEBS Letters
Volume594
Nummer van het tijdschrift21
DOI's
StatusGepubliceerd - nov 2020

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