Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C.
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.
1] The Francis Crick Institute, London, UK. [2] UCL Genetics Institute, University College London, London, UK.
Borbala
B
Mifsud
The Francis Crick Institute, London, UK.
Filipe
F
Tavares-Cadete
Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK.
Alice N
AN
Young
The Francis Crick Institute, London, UK.
Robert
0000000322749517
R
Sugar
Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK.
Stefan
S
Schoenfelder
Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK.
Lauren
L
Ferreira
Bioinformatics Group, Babraham Institute, Cambridge, UK.
Steven W
SW
Wingett
Bioinformatics Group, Babraham Institute, Cambridge, UK.
Simon
S
Andrews
Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.
William
W
Grey
Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK.
Philip A
0000000341012502
PA
Ewels
Diagnostics and Genomics Division, Agilent Technologies, Santa Clara, California, USA.
Bram
B
Herman
Diagnostics and Genomics Division, Agilent Technologies, Santa Clara, California, USA.
Scott
S
Happe
Diagnostics and Genomics Division, Agilent Technologies, Santa Clara, California, USA.
Andy
A
Higgs
Diagnostics and Genomics Division, Agilent Technologies, Santa Clara, California, USA.
Emily
E
LeProust
Department of Haematology, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.
George A
GA
Follows
Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK.
Peter
P
Fraser
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.
Nicholas M
NM
Luscombe
1] Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK. [2] Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.
Cameron S
CS
Osborne
D002460:Cell Line; D002874:Chromosome Mapping; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic