Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C
| Autor: | Stefan Schoenfelder, Steven W. Wingett, Philip Ewels, George A. Follows, Emily M LeProust, Nicholas M. Luscombe, Simon Andrews, Alice N Young, Andy Higgs, Robert Sugar, Borbala Mifsud, Lauren Ferreira, Filipe Tavares-Cadete, Scott Happe, Cameron S. Osborne, Bram Herman, William Grey, Peter Fraser |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Regulation of gene expression
Genetics Genome Human Chromosome Mapping Promoter Epistasis Genetic Biology Genome Polymorphism Single Nucleotide Cell Line Chromosome conformation capture Gene Expression Regulation Humans Human genome Gene Regulatory Networks Enhancer Promoter Regions Genetic Gene Functional genomics |
| Zdroj: | Nature genetics. 47(6) |
| ISSN: | 1546-1718 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|