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Nat Genet. 2015 Jun;47(6):598-606. doi: 10.1038/ng.3286. Epub 2015 May 4.

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

Author information

1
1] The Francis Crick Institute, London, UK. [2] UCL Genetics Institute, University College London, London, UK.
2
The Francis Crick Institute, London, UK.
3
Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK.
4
Bioinformatics Group, Babraham Institute, Cambridge, UK.
5
Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.
6
Diagnostics and Genomics Division, Agilent Technologies, Santa Clara, California, USA.
7
Department of Haematology, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.
8
1] The Francis Crick Institute, London, UK. [2] UCL Genetics Institute, University College London, London, UK. [3] Okinawa Institute of Science and Technology, Okinawa, Japan.
9
1] Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK. [2] Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.

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.

PMID:
25938943
DOI:
10.1038/ng.3286
[Indexed for MEDLINE]

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