Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Javierre, BM; Burren, OS; Wilder, SP; Kreuzhuber, R; Hill, SM; Sewitz, S; Cairns, J; Wingett, SW; Várnai, C; Thiecke, MJ; Burden, F; Farrow, S; Cutler, AJ; Rehnström, K; Downes, K; Grassi, L; Kostadima, M; Freire-Pritchett, P; Wang, F; BLUEPRINT Consortium, ; Stunnenberg, HG; Todd, JA; Zerbino, DR; Stegle, O; Ouwehand, WH; Frontini, M; Wallace, C; Spivakov, M; Fraser, P

Published Date

  • November 17, 2016

Published In

Volume / Issue

  • 167 / 5

Start / End Page

  • 1369 - 1384.e19

PubMed ID

  • 27863249

Pubmed Central ID

  • PMC5123897

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2016.09.037


  • eng

Conference Location

  • United States