viernes, 22 de mayo de 2015

Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C : Nature Genetics : Nature Publishing Group

Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C : Nature Genetics : Nature Publishing Group



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

Nature Genetics
 
 
doi:10.1038/ng.3286
Received
 
Accepted
 
Published online
 

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.

At a glance

Figures

left
  1. Schematic of the principles of CHi-C.
    Figure 1
  2. Numbers and separation distances of promoter interactions in GM12878 cells.
    Figure 2
  3. Promoter interactions and genome organization.
    Figure 3

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