Abstract

Although the locations of promoters and enhancers have been identified in several cell types, we still have limited information on their connectivity. We developed HiCap, which combines a 4-cutter restriction enzyme Hi-C with sequence capture of promoter regions. Applying the method to mouse embryonic stem cells, we identified promoter-anchored interactions involving 15,905 promoters and 71,984 distal regions. The distal regions were enriched for enhancer marks and transcription, and had a mean fragment size of only 699 bp — close to single-enhancer resolution. High-resolution maps of promoter-anchored interactions with HiCap will be important for detailed characterizations of chromatin interaction landscapes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0727-9) contains supplementary material, which is available to authorized users.

Highlights

  • Enhancers are cis-acting DNA elements, essential for the regulation of transcription at nearby genes [1]

  • Numerous methods exist for the genome-wide mapping of enhancers, e.g., STARR-seq [2] and ChIP-seq for transcription factors (TFs) [3], co-factors [4], chromatin modifications [5], and DNA hypersensitive sites [6], it is still challenging to globally identify the promoters regulated by each enhancer

  • Development of HiCap To identify genome-wide interactions anchored on promoters, we started by experimenting with chromatin conformation capture (3C) and Hi-C procedures together with sequence capture of promoter regions

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Summary

Introduction

Enhancers are cis-acting DNA elements, essential for the regulation of transcription at nearby genes [1]. Numerous methods exist for the genome-wide mapping of enhancers, e.g., STARR-seq [2] and ChIP-seq for transcription factors (TFs) [3], co-factors [4], chromatin modifications [5], and DNA hypersensitive sites [6], it is still challenging to globally identify the promoters regulated by each enhancer. Genome-wide chromatin interaction was first studied de novo with the development of Hi-C [11] that selected for ligated fragments without using any particular regions as baits. This method was successfully used to identify topological domains and higher-order

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