Landscape of cohesin-mediated chromatin loops in the human genome

F Grubert, R Srivas, DV Spacek, M Kasowski… - Nature, 2020 - nature.com
F Grubert, R Srivas, DV Spacek, M Kasowski, M Ruiz-Velasco, N Sinnott-Armstrong
Nature, 2020nature.com
Physical interactions between distal regulatory elements have a key role in regulating gene
expression, but the extent to which these interactions vary between cell types and contribute
to cell-type-specific gene expression remains unclear. Here, to address these questions as
part of phase III of the Encyclopedia of DNA Elements (ENCODE), we mapped cohesin-
mediated chromatin loops, using chromatin interaction analysis by paired-end tag
sequencing (ChIA-PET), and analysed gene expression in 24 diverse human cell types …
Abstract
Physical interactions between distal regulatory elements have a key role in regulating gene expression, but the extent to which these interactions vary between cell types and contribute to cell-type-specific gene expression remains unclear. Here, to address these questions as part of phase III of the Encyclopedia of DNA Elements (ENCODE), we mapped cohesin-mediated chromatin loops, using chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), and analysed gene expression in 24 diverse human cell types, including core ENCODE cell lines. Twenty-eight per cent of all chromatin loops vary across cell types; these variations modestly correlate with changes in gene expression and are effective at grouping cell types according to their tissue of origin. The connectivity of genes corresponds to different functional classes, with housekeeping genes having few contacts, and dosage-sensitive genes being more connected to enhancer elements. This atlas of chromatin loops complements the diverse maps of regulatory architecture that comprise the ENCODE Encyclopedia, and will help to support emerging analyses of genome structure and function.
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