This is the final version of the article. It first appeared from Elsevier (Cell Press) via https://doi.org/10.1016/j.cell.2016.09.03

Burden, Frances

Burren, Oliver S

Cairns, Jonathan

Cutler, Antony J

Downes, Kate

Farrow, Samantha

Fraser, Peter

Freire-Pritchett, Paula

Frontini, Mattia

Grassi, Luigi

Hill, Steven M

Javierre, Biola M

Kostadima, Myrto

Kreuzhuber, Roman

Ouwehand, Willem Hendrik

Rehnstrom, Karola

Sewitz, Sven

Spivakov, Mikhail

Stegle, Oliver

Stunnenberg, Hendrik G

The, BLUEPRINT Consortium

Thiecke, Michiel J

Todd, John A

Várnai, Csilla

Wallace, Chris

Wang, Fan

Wilder, Steven P

Wingett, Steven W

Zerbino, Daniel R

Cell

PubMed

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

Javierre, BM

Burren, OS

Wilder, SP

Kreuzhuber, R

Hill, SM

Sewitz, S

Cairns, J

Wingett, SW

Varnai, C

Thiecke, MJ

Burden, F

Farrow, S

Cutler, AJ

Rehnstrom, K

Downes, K

Grassi, L

Kostadima, M

Freire-Pritchett, P

Wang, F

Stunnenberg, HG

Todd, JA

Zerbino, DR

Stegle, O

Ouwehand, WH

Frontini, M

Wallace, C

Spivakov, M

Fraser, P

UCL Discovery

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

University of Birmingham Research Portal

English

Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters

Contains fulltext :
                  161816.pdf (publisher's version ) (Open Access

Javierre, B.M.

Burren, O.S.

Wilder, S.P.

Kreuzhuber, R.

Hill, S.M.

Sewitz, S.

Cairns, J.

Wingett, S.W.

Varnai, C.

Thiecke, M.J.

Burden, F.

Farrow, S.

Cutler, A.J.

Rehnstrom, K.

Downes, K.

Grassi, L.

Kostadima, M.

Freire-Pritchett, P.

Stunnenberg, H.

Todd, J.A.

Zerbino, D.R.

Stegle, O.

Ouwehand, W.H.

Frontini, M.

Wallace, C.

Spivakov, M.

Fraser, P.

Radboud Repository

Várnai, C

Rehnström, K

BLUEPRINT Consortium

Oxford University Research Archive (ORA)

Cutler, Antony

Todd, John

ORA - Oxford University Research Archive

NARCIS 

http://dx.doi.org/10.1016/j.cell.2016.09.037

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

Abstract

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UCL Discovery

University of Birmingham Research Portal

Radboud Repository

Oxford University Research Archive (ORA)

ORA - Oxford University Research Archive

University of Birmingham Research Portal

NARCIS