期刊
NATURE GENETICS
卷 47, 期 6, 页码 598-606出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3286
关键词
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资金
- Leukaemia and Lymphoma Research Fellowship
- Framework Programme 7 Epigenesys Network of Excellence
- Cancer Research UK
- UCL
- OIST
- Wellcome Trust
- BBSRC [BBS/E/B/000C0405, BBS/E/B/000C0404, BBS/E/B/0000M738, BBS/E/B/0000H212] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000M738, BBS/E/B/000C0404, BBS/E/B/0000H212, BBS/E/B/000C0405] Funding Source: researchfish
- Cancer Research UK [16358] Funding Source: researchfish
- The Francis Crick Institute [10111, 10110] Funding Source: researchfish
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.
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