Journal
CELL
Volume 167, Issue 5, Pages 1369-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2016.09.037
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Funding
- UK Medical Research Council [MR/L007150/1, MC_UP_1302/1, MC_UP_1302/3, MC_UP_1302/5]
- UK Biotechnology and Biological Sciences Research Council [BB/J004480/1]
- ERC (DEVOCHROMO advanced grant)
- JDRF [9-2011-253, 5-SRA-2015-130]
- Wellcome Trust [089989, 091157, 095908, 100140, 107212, 107881]
- European Union 7th Framework Programme (FP7) [241447, 282510]
- NHS Blood and Transplant
- NIHR [PG-0310-1002]
- BHF [RG/09/12/28096]
- NHS Health Education England
- BHF Cambridge Centre of Excellence [RE/13/6/30180]
- European Molecular Biology Laboratory
- BBSRC [BBS/E/B/000M0816] Funding Source: UKRI
- MRC [MR/L007150/1, MC_UU_00002/4] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/B/000M0816] Funding Source: researchfish
- British Heart Foundation [RG/09/012/28096] Funding Source: researchfish
- Medical Research Council [MR/L007150/1, MC_UU_00002/4, MC_UP_1302/5] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10275, RP-PG-0310-1002, NF-SI-0513-10151, NF-SI-0513-10143, NF-SI-0510-10214] Funding Source: researchfish
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Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers. Promoter interactomes reflect lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched in genetic variants linked with altered expression of genes they contact, highlighting their functional role. We exploit this rich resource to connect non-coding disease variants to putative target promoters, prioritizing thousands of disease-candidate genes and implicating disease pathways. Our results demonstrate the power of primary cell promoter interactomes to reveal insights into genomic regulatory mechanisms underlying common diseases.
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