Publication

Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C.

current
   March 28th, 2019 at 3:01pm

Overview


Abstract

Transcriptional control in large genomes often requires looping interactions between distal DNA elements, such as enhancers and target promoters. Current chromosome conformation capture techniques do not offer sufficiently high resolution to interrogate these regulatory interactions on a genomic scale. Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types. We identify over 1.6 million shared and cell type-restricted interactions spanning hundreds of kilobases between promoters and distal loci. Transcriptionally active genes contact enhancer-like elements, whereas transcriptionally inactive genes interact with previously uncharacterized elements marked by repressive features that may act as long-range silencers. Finally, we show that interacting loci are enriched for disease-associated SNPs, suggesting how distal mutations may disrupt the regulation of relevant genes. This study provides new insights and accessible tools to dissect the regulatory interactions that underlie normal and aberrant gene regulation.

Authors

Mifsud B  •  Tavares-Cadete F  •  Young AN  •  Sugar R  •  Schoenfelder S  •  Ferreira L  •  Wingett SW  •  Andrews S  •  Grey W  •  Ewels PA  •  Herman B  •  Happe S  •  Higgs A  •  LeProust E  •  Follows GA  •  Fraser P  •  Luscombe NM  •  Osborne CS

Link

https://www.ncbi.nlm.nih.gov/pubmed/25938943


Journal

Nature genetics

PMID:25938943

Published

June 2015