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

Publication ,  Journal Article
Javierre, BM; Burren, OS; Wilder, SP; Kreuzhuber, R; Hill, SM; Sewitz, S; Cairns, J; Wingett, SW; Várnai, C; Thiecke, MJ; Burden, F; Farrow, S ...
Published in: Cell
November 17, 2016

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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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

November 17, 2016

Volume

167

Issue

5

Start / End Page

1369 / 1384.e19

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Humans
  • Hematopoiesis
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Epigenomics
  • Enhancer Elements, Genetic
  • Disease
 

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Javierre, B. M., Burren, O. S., Wilder, S. P., Kreuzhuber, R., Hill, S. M., Sewitz, S., … Fraser, P. (2016). Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters. Cell, 167(5), 1369-1384.e19. https://doi.org/10.1016/j.cell.2016.09.037
Javierre, Biola M., Oliver S. Burren, Steven P. Wilder, Roman Kreuzhuber, Steven M. Hill, Sven Sewitz, Jonathan Cairns, et al. “Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.Cell 167, no. 5 (November 17, 2016): 1369-1384.e19. https://doi.org/10.1016/j.cell.2016.09.037.
Javierre BM, Burren OS, Wilder SP, Kreuzhuber R, Hill SM, Sewitz S, et al. Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters. Cell. 2016 Nov 17;167(5):1369-1384.e19.
Javierre, Biola M., et al. “Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.Cell, vol. 167, no. 5, Nov. 2016, pp. 1369-1384.e19. Pubmed, doi:10.1016/j.cell.2016.09.037.
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. Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters. Cell. 2016 Nov 17;167(5):1369-1384.e19.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

November 17, 2016

Volume

167

Issue

5

Start / End Page

1369 / 1384.e19

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Humans
  • Hematopoiesis
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Epigenomics
  • Enhancer Elements, Genetic
  • Disease